Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait

NCT04310059 | Not Yet Recruiting

• 1 other identifier: UW 20-084
• Study Type: interventional
• Target: 270
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Thalassemia; Folic Acid Deficiency Anemia

Outcome Measures

Primary Outcomes (5)

• Haemoglobin level

  Change in level throughout the pregnancy, up to 42 weeks

• Maternal RBC folate concentration

  Change in level throughout the pregnancy, up to 42 weeks

• Maternal serum folate concentration

  Change in level throughout the pregnancy, up to 42 weeks

• Cord blood RBC

  Upon birth

• Cord blood serum folate concentration

  Upon birth

Secondary Outcomes (3)

• Ferritin level

  Change in level throughout the pregnancy, up to 42 weeks

• Maternal Vitamin B12

  Maternal Vitamin B12 at first antenatal visit

• Cord blood vitamin B12

  Cord blood vitamin B12 upon birth

Study Arms (3)

Folic acid 5mg

ACTIVE COMPARATOR

Dietary Supplement: Folic acid

Folic acid 0.5mg

ACTIVE COMPARATOR

Dietary Supplement: Folic acid

Materna

ACTIVE COMPARATOR

Dietary Supplement: Materna

Interventions

Folic acid DIETARY_SUPPLEMENT

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)

Folic acid 0.5mg; Folic acid 5mg

Materna DIETARY_SUPPLEMENT

Materna

Materna

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only pregnant women are recruited
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Singleton pregnancy
• Alpha thalassaemia trait
• Beta thalassaemia trait

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead
• Queen Mary Hospital, Hong Kong: collaborator

Related Publications (19)

• Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and neural tube defects. Implications for prevention. JAMA. 1995 Dec 6;274(21):1698-702. doi: 10.1001/jama.1995.03530210052030.

  PMID: 7474275 BACKGROUND

• Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. doi: 10.1056/NEJM199212243272602.

  PMID: 1307234 BACKGROUND

• Crider KS, Devine O, Hao L, Dowling NF, Li S, Molloy AM, Li Z, Zhu J, Berry RJ. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014 Jul 29;349:g4554. doi: 10.1136/bmj.g4554.

  PMID: 25073783 BACKGROUND

• US Preventive Services Task Force; Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW Jr, Garcia FA, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phillips WR, Phipps MG, Pignone MP, Silverstein M, Tseng CW. Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement. JAMA. 2017 Jan 10;317(2):183-189. doi: 10.1001/jama.2016.19438.

  PMID: 28097362 BACKGROUND

• Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep. 2015 Apr 24;64(15):421-3.

  PMID: 25905896 BACKGROUND

• Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 Jul 20;338(8760):131-7.

  PMID: 1677062 BACKGROUND

• Management of Beta Thalassaemia in Pregnancy. Green-top Guideline No 66: Royal College of Obstetricians & Gynaecologists; 2014. p. 1-17.

  BACKGROUND

• Lao TT. Obstetric care for women with thalassemia. Best Pract Res Clin Obstet Gynaecol. 2017 Feb;39:89-100. doi: 10.1016/j.bpobgyn.2016.09.002. Epub 2016 Sep 23.

  PMID: 28341055 BACKGROUND

• Leung CF, Lao TT, Chang AM. Effect of folate supplement on pregnant women with beta-thalassaemia minor. Eur J Obstet Gynecol Reprod Biol. 1989 Dec;33(3):209-13. doi: 10.1016/0028-2243(89)90131-7.

  PMID: 2599250 BACKGROUND

• Plumptre L, Masih SP, Ly A, Aufreiter S, Sohn KJ, Croxford R, Lausman AY, Berger H, O'Connor DL, Kim YI. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr. 2015 Oct;102(4):848-57. doi: 10.3945/ajcn.115.110783. Epub 2015 Aug 12.

  PMID: 26269367 BACKGROUND

• Caudill MA, Cruz AC, Gregory JF 3rd, Hutson AD, Bailey LB. Folate status response to controlled folate intake in pregnant women. J Nutr. 1997 Dec;127(12):2363-70. doi: 10.1093/jn/127.12.2363.

  PMID: 9405587 BACKGROUND

• Baghersalimi A, Hemmati Kolachahi H, Darbandi B, Kamran Mavardiani Z, Alizadeh Alinodehi M, Dalili S, Hassanzadeh Rad A. Assessment of Serum Folic Acid and Homocysteine in Thalassemia Major Patients Before and After Folic Acid Supplement Cessation. J Pediatr Hematol Oncol. 2018 Oct;40(7):504-507. doi: 10.1097/MPH.0000000000001295.

  PMID: 30124548 BACKGROUND

• Tripathi G, Kalra M, Mahajan A. Folate supplementation in transfusion-dependent thalassemia: Do we really need such high doses? Indian J Med Paediatr Oncol. 2016 Oct-Dec;37(4):305. doi: 10.4103/0971-5851.195746. No abstract available.

  PMID: 28144102 BACKGROUND

• Tso SC, Wong RL. Folate status in pregnant Chinese women in Hong Kong. Int J Gynaecol Obstet. 1980;18(4):290-4. doi: 10.1002/j.1879-3479.1980.tb00498.x.

  PMID: 6109674 BACKGROUND

• White JM, Richards R, Byrne M, Buchanan T, White YS, Jelenski G. Thalassaemia trait and pregnancy. J Clin Pathol. 1985 Jul;38(7):810-7. doi: 10.1136/jcp.38.7.810.

  PMID: 4019802 BACKGROUND

• Guideline: Fortification of Rice with Vitamins and Minerals as a Public Health Strategy. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK531762/

  PMID: 30307723 BACKGROUND

• Atta CA, Fiest KM, Frolkis AD, Jette N, Pringsheim T, St Germaine-Smith C, Rajapakse T, Kaplan GG, Metcalfe A. Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis. Am J Public Health. 2016 Jan;106(1):e24-34. doi: 10.2105/AJPH.2015.302902. Epub 2015 Nov 12.

  PMID: 26562127 BACKGROUND

• Joseph CA, Dedman D, Fern K, Chakraverty P, Watson JM. Influenza surveillance in England and Wales: November 1991-June 1992. Commun Dis Rep CDR Rev. 1992 Dec 4;2(13):R149-52. No abstract available.

  PMID: 1285133 BACKGROUND

• Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Relief of uremic pruritus with ultraviolet phototherapy. N Engl J Med. 1977 Jul 21;297(3):136-8. doi: 10.1056/NEJM197707212970304.

  PMID: 865585 BACKGROUND

MeSH Terms

Conditions

Thalassemia

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Pui Wah Hui, MD

CONTACT

852-22553402; apwhui@hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 17, 2020
• Study Start: July 1, 2024
• Primary Completion: July 31, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share