Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait
Primary Purpose
Thalassemia, Folic Acid Deficiency Anemia
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Folic acid
Materna
Sponsored by
About this trial
This is an interventional prevention trial for Thalassemia
Eligibility Criteria
Inclusion Criteria:
- Singleton pregnancy
- Alpha thalassaemia trait
- Beta thalassaemia trait
Exclusion Criteria:
- Women taking over 0.6mg folic acid daily for 3 months or more prior to and during pregnancy
- Gestational age > 16 weeks at first antenatal visit
- Women age =< 18 years old
- Booking BMI =< 18 or >= 35
- Serum ferritin level < 30ug/L or 68 pmol/L
- Concomitant alpha and beta thalassaemia
- Hb H disease
- Beta thalassaemia major
- Beta thalassaemia intermediate
- Thalassaemia other than alpha or beta type
- Women on long term medications
- Women with risk factors for NTD
- Women with known epilepsy
- Women with bariatric surgery or malabsorption diseases
- Women with known MTHFR polymorphism
- Vegetarian
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Folic acid 5mg
Folic acid 0.5mg
Materna
Arm Description
Outcomes
Primary Outcome Measures
Haemoglobin level
Maternal RBC folate concentration
Maternal serum folate concentration
Cord blood RBC
Cord blood serum folate concentration
Secondary Outcome Measures
Ferritin level
Maternal Vitamin B12
Cord blood vitamin B12
Full Information
NCT ID
NCT04310059
First Posted
March 5, 2020
Last Updated
May 9, 2023
Sponsor
The University of Hong Kong
Collaborators
Queen Mary Hospital, Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT04310059
Brief Title
Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait
Official Title
A Randomized Controlled Trial to Study the Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Hong Kong
Collaborators
Queen Mary Hospital, Hong Kong
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Folic acid supplementation has been recommended for prevention of neural tube defects in pregnancy when taken periconceptionally up to 12 weeks of gestation. A daily dose of 0.4mg has been endorsed by World Health Organisation to achieve a Red blood cell (RBC) folate level of 906nmol/L (400ng/mL) for reduction of neural tube defect. Hong Kong has no policy on food fortification. Research data conducted in countries with food fortification may not be applicable. It is therefore essential to study the baseline folate status in pregnant women locally.
For pregnant women with thalassaemia, they are believed to have a higher risk of folate deficiency because of an increased rate of erythropoiesis and chronic haemolysis. However, information on folate level of thalassaemia trait in pregnancy is scanty. Unmetabolized folic acid has been detected in maternal and fetal blood when daily dosage greater than 0.8-1mg was taken. In term of the dosage and duration of folic acid supplementation after 12 weeks of gestation, the practice varies widely among public hospitals and Maternity & Child Health Care centres. It is therefore essential to study the optimal dosage of folic acid supplementation in women with thalassaemia.
Detailed Description
Folic acid supplementation is well established for its role in prevention of neural tube defects (NTD) when taken periconceptionally up to 12 weeks of gestation. The naturally occurring form, folate, is a water soluble B vitamin (B9) that is mostly present in dark green leafy vegetables and legumes. However, it is only 50% bioavailable. Folic acid, on the contrary, as a synthetic form of folate is almost completely bioavailable especially when administered in an empty stomach. It has been endorsed by World Health Organisation that RBC folate cutoff of 906 nmol/L (400ng/mL) is required for reduction of NTD. This level is only achievable by taking Folic acid supplementation of 0.4mg/day. Women at higher risk of having recurrent NTD is recommended to take higher dose at 4mg/day.
Patients with thalassaemia have an increased rate of erythropoiesis and chronic haemolysis. They are believed to have a higher rate of folate turnover and consequentially higher risk of folate deficiency. Guideline from Royal College of Obstetricians and Gynaecologists recommends daily intake of 5mg folic acid preconceptionally to prevent NTD. But, it does not specify whether this dosage is applicable to all types and degrees of thalassaemias and research data on the optimal dosage is lacking.
In addition to prevention of NTD, the supplementation of folic acid is also recommended for pregnant thalassaemia women for prevention of antenatal anaemia. In a retrospective study of Chinese population reported in 1989, women with beta-thalassaemia minor taking additional 5mg folic acid had higher pre-delivery haemoglobin concentration of 10.1 g/dL compared to haemoglobin level of 9.7 g/dL in the group taking Obimin (a pregnancy supplement containing 0.25mg folic acid and 90 mg ferrous fumarate). However, there was no further randomised controlled trial to validate this observation. Though a higher folic acid supplementation was believed to be beneficial in prevention of antenatal anaemia, unmetabolized folic acid were detected in maternal and fetal blood when daily dosage greater than 0.8-1mg was taken. Moreover, a higher rate of urinary excretion of folic acid was also observed in pregnant women receiving higher dosage of folic acid supplementation.
In non-pregnant beta thalassaemia major patients, folic acid supplementation at 1 mg daily was advised as cessation of which could lead to a significant reduction in serum folate. This has been counter-proposed by the observation of normal to high serum folate levels in transfusion dependent thalassaemia receiving optimal transfusion. Indeed, folic acid supplementation should be considered for non-transfusion dependent thalassaemia as excessive erythropoiesis is required to maintain satisfactory haemoglobin.
Folate level drops during pregnancy to puerperal period. Information on folate level of thalassaemia trait in pregnancy is scanty. In a paper published in 1985, no difference in serum folate was found between normal women and women with thalassaemia trait, and hence usual supplementation was suggested.
Hong Kong has no policy on food fortification. Research data conducted in countries with food fortification may not be applicable. The folate status may have been changed in last few decades because of better general nutritional status and public knowledge of preconception folic acid supplementation. The preparation of 5mg folic acid is available in all public hospitals and preparation of 0.5mg folic acid is recently introduced. As such, the 5mg folic acid prescription is traditionally adopted and this can be a result of its availability. However, the practice varies widely among public hospitals and Maternity & Child Health Care centres. There is no standardised guideline on the dosage and indications of folic acid supplementation for pregnant thalassaemic women. More importantly, no recent data on the baseline folate status in pregnant women with thalassaemia is available locally.
Patient blood management in Obstetrics has been advocated with an aim to minimize blood loss by maintaining haemoglobin levels, reduce blood transfusion and optimize patient outcome. Identification and treatment of maternal anaemia is one of the three main pillars to achieve it. Even though thalassaemia can be considered as a risk factor for NTD, it remains controversial as to how much folic acid supplementation is adequate for pregnant women with thalassaemia trait in prevention of maternal anaemia which is a key element in maternity care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thalassemia, Folic Acid Deficiency Anemia
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
270 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Folic acid 5mg
Arm Type
Active Comparator
Arm Title
Folic acid 0.5mg
Arm Type
Active Comparator
Arm Title
Materna
Arm Type
Active Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Folic acid
Intervention Description
women will be randomised into one of the three groups. Group A - Folic acid 5mg/day Group B - Folic acid 0.5mg/day Group C - Materna one tablet/day (a pregnancy supplement containing 0.6mg folic acid)
Intervention Type
Dietary Supplement
Intervention Name(s)
Materna
Intervention Description
Materna
Primary Outcome Measure Information:
Title
Haemoglobin level
Time Frame
Change in level throughout the pregnancy, up to 42 weeks
Title
Maternal RBC folate concentration
Time Frame
Change in level throughout the pregnancy, up to 42 weeks
Title
Maternal serum folate concentration
Time Frame
Change in level throughout the pregnancy, up to 42 weeks
Title
Cord blood RBC
Time Frame
Upon birth
Title
Cord blood serum folate concentration
Time Frame
Upon birth
Secondary Outcome Measure Information:
Title
Ferritin level
Time Frame
Change in level throughout the pregnancy, up to 42 weeks
Title
Maternal Vitamin B12
Time Frame
Maternal Vitamin B12 at first antenatal visit
Title
Cord blood vitamin B12
Time Frame
Cord blood vitamin B12 upon birth
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Only pregnant women are recruited
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Singleton pregnancy
Alpha thalassaemia trait
Beta thalassaemia trait
Exclusion Criteria:
Women taking over 0.6mg folic acid daily for 3 months or more prior to and during pregnancy
Gestational age > 16 weeks at first antenatal visit
Women age =< 18 years old
Booking BMI =< 18 or >= 35
Serum ferritin level < 30ug/L or 68 pmol/L
Concomitant alpha and beta thalassaemia
Hb H disease
Beta thalassaemia major
Beta thalassaemia intermediate
Thalassaemia other than alpha or beta type
Women on long term medications
Women with risk factors for NTD
Women with known epilepsy
Women with bariatric surgery or malabsorption diseases
Women with known MTHFR polymorphism
Vegetarian
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pui Wah Hui, MD
Phone
852-22553402
Email
apwhui@hku.hk
12. IPD Sharing Statement
Plan to Share IPD
No
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7474275
Citation
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Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait
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