Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Mar 28;2013(3):CD006896.
doi: 10.1002/14651858.CD006896.pub2.

Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes

Zohra S Lassi  1 , Rehana A Salam, Batool A Haider, Zulfiqar A Bhutta
Affiliations
Review

Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes

Zohra S Lassi et al. Cochrane Database Syst Rev. .

Abstract

Background: During pregnancy, fetal growth causes an increase in the total number of rapidly dividing cells, which leads to increased requirements for folate. Inadequate folate intake leads to a decrease in serum folate concentration, resulting in a decrease in erythrocyte folate concentration, a rise in homocysteine concentration, and megaloblastic changes in the bone marrow and other tissues with rapidly dividing cells

Objectives: To assess the effectiveness of oral folic acid supplementation alone or with other micronutrients versus no folic acid (placebo or same micronutrients but no folic acid) during pregnancy on haematological and biochemical parameters during pregnancy and on pregnancy outcomes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2012) and we contacted major organisations working in micronutrient supplementation, including UNICEF Nutrition Section, World Health Organization (WHO) Maternal and Reproductive Health, WHO Nutrition Division, and National Center on Birth defects and Developmnetal Disabilities, US Centers for Disease Control and Prevention (CDC).

Selection criteria: All randomised, cluster-randomised and cross-over controlled trials evaluating supplementation of folic acid alone or with other micronutrients versus no folic acid (placebo or same micronutrients but no folic acid) in pregnancy.

Data collection and analysis: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy.

Main results: Thirty-one trials involving 17,771 women are included in this review. This review found that folic acid supplementation has no impact on pregnancy outcomes such as preterm birth (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.38; three studies, 2959 participants), and stillbirths/neonatal deaths (RR 1.33, 95% CI 0.96 to 1.85; three studies, 3110 participants). However, improvements were seen in the mean birthweight (mean difference (MD) 135.75, 95% CI 47.85 to 223.68). On the other hand, the review found no impact on improving pre-delivery anaemia (average RR 0.62, 95% CI 0.35 to 1.10; eight studies, 4149 participants; random-effects), mean pre-delivery haemoglobin level (MD -0.03, 95% CI -0.25 to 0.19; 12 studies, 1806 participants), mean pre-delivery serum folate levels (standardised mean difference (SMD) 2.03, 95% CI 0.80 to 3.27; eight studies, 1250 participants; random-effects), and mean pre-delivery red cell folate levels (SMD 1.59, 95% CI -0.07 to 3.26; four studies, 427 participants; random-effects). However, a significant reduction was seen in the incidence of megaloblastic anaemia (RR 0.21, 95% CI 0.11 to 0.38, four studies, 3839 participants).

Authors' conclusions: We found no conclusive evidence of benefit of folic acid supplementation during pregnancy on pregnancy outcomes.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Funnel plot of comparison: 1 Folic acid versus no folic acid, outcome: 1.7 Mean pre‐delivery haemoglobin level.
1.1
1.1. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 1 Preterm birth.
1.2
1.2. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 2 Stillbirths/neonatal deaths.
1.3
1.3. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 3 Low birthweight.
1.4
1.4. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 4 Mean birthweight (g).
1.5
1.5. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 5 Mean birth weight (sensitivity analysis‐after removing Trigg 1976).
1.6
1.6. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 6 Pre‐delivery anaemia.
1.7
1.7. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 7 Mean pre‐delivery haemoglobin level.
1.8
1.8. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 8 Mean pre‐delivery haemoglobin level.
1.9
1.9. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 9 Mean pre‐delivery serum folate.
1.10
1.10. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 10 Mean pre‐delivery serum folate.
1.11
1.11. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 11 Low pre‐delivery serum folate.
1.12
1.12. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 12 Mean red cell folate.
1.13
1.13. Analysis
Comparison 1 Folic acid versus no folic acid, Outcome 13 Megaloblastic anaemia.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD006896

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Balmelli 1974 {published data only}
    1. Balmelli GP, Huser HJ. Folic acid deficiency in pregnant women in Switzerland [Zur Frage des Folsäuremangels bei Schwangeren in der Schweiz]. Schweizerische Medizinische Wochenschrift 1974;104(10):351‐6. - PubMed
Batu 1976 {published data only}
    1. Batu AT, Toe T, Pe H, Nyunt KK. A prophylactic trial of iron and folic acid supplements in pregnant Burmese women. Israel Journal of Medical Sciences 1976;12:1410‐7. - PubMed
Baumslag 1970 {published data only}
    1. Baumslag N, Edelstein T, Metz J. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. British Medical Journal 1970;1:16‐7. - PMC - PubMed
Blot 1981 {published data only}
    1. Blot I, Papiernik E, Kaltwasser JP, Werner E, Tchernia G. Influence of routine administration of folic acid and iron during pregnancy. Gynecologic and Obstetric Investigation 1981;12:294‐304. - PubMed
Castren 1968 {published data only}
    1. Castren O, Levanto A, Rauramo L, Ruponen S. Preventive iron and folic acid therapy in pregnancy. Annales Chirurgiae et Gynaecologiae Fenniae 1968;57:382‐6. - PubMed
Chanarin 1965 {published data only}
    1. Chanarin I, Rothman D, Berry V. Iron deficiency and its relation to folic‐acid status in pregnancy: results of a clinical trial. British Medical Journal 1965;1:480‐5. - PMC - PubMed
Chanarin 1968 {published data only}
    1. Chanarin I, Rothman D, Ward A, Perry J. Folate status and requirement in pregnancy. British Medical Journal 1968;2:390‐4. - PMC - PubMed
Charles 2005 {published data only}
    1. Charles D, Ness AR, Campbell D, Smith GD, Hall MH. Taking folate in pregnancy and risk of maternal breast cancer. BMJ 2004;329(7479):1375‐6. - PMC - PubMed
    1. Charles DHM, Ness AR, Campbell D, Smith GD, Whitely E, Hall MH. Folic acid supplements in pregnancy and birth outcome: re‐analysis of a large randomised controlled trial and update of Cochrane review. Pediatric and Perinatal Epidemiology 2005;19:112‐24. - PubMed
    1. Hall M. Assessment of the effects of folic acid deficiency in pregnancy. [MD thesis]. University of Aberdeen, 1970.
    1. Hall MH. Folic acid deficiency and abruptio placentae. Journal of Obstetric and Gynaecology 1972;79:222‐5. - PubMed
    1. Hall MH, Pirani BB, Campbell D. The cause of the fall in serum folate in normal pregnancy. British Journal of Obstetrics and Gynaecology 1976;83:132‐6. - PubMed
Chisholm 1966 {published data only}
    1. Chisholm M. A controlled clinical trial of prophylactic folic acid and iron in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1966;73:191‐6.
Christian 2003 {published data only}
    1. Christian P, Darmstadt GL, Wu L, Khatry SK, Leclerq SC, Katz J, et al. The effect of maternal micronutrient supplementation on early neonatal morbidity in rural Nepal: a randomised, controlled, community trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(8):660‐4. - PubMed
    1. Christian P, Jiang T, Khatry SK, LeClerq SC, Shrestha SR, West Jr KP. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. American Journal of Clinical Nutrition 2006;83:788‐94. - PubMed
    1. Christian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, et al. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ 2003;326(7389):571. - PMC - PubMed
    1. Christian P, Khatry SK, LeClerq SC, Dali SM. Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal. International Journal of Gynecology & Obstetrics 2009;106(1):3‐7. - PubMed
    1. Christian P, Murray‐Kolb LE, Khatry SK, Katz J, Schaefer BA, Cole PM, et al. Prenatal micronutrient supplementation and intellectual and motor function in early school‐aged children in Nepal. JAMA 2010;304(24):2716‐23. - PubMed
Dawson 1962 {published data only}
    1. Dawson DW, More JRS, Aird DC. Prevention of megaloblastic anaemia in pregnancy by folic acid. Lancet 1962;2:1015‐20. - PubMed
Decsi 2005 {published data only}
    1. Broekaert I, Campoy C, Iznaola C, Hoffman B, Mueller‐Felber W, Koletzko BV. Visual evoked potentials in infants after dietary supply of docosahexaenoic acid and 5‐methyl‐tetrahydrofolate during pregnancy. Journal of Pediatric Gastroenterology and Nutrition 2004;39(Suppl 1):S33.
    1. Campoy C, Escolano‐Margarit MV, Ramos R, Parrilla‐Roure M, Csabi G, Beyer J, et al. Effects of prenatal fish‐oil and 5‐methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. American Journal of Clinical Nutrition 2011;94(6 Suppl):1880S‐8S. - PubMed
    1. Campoy C, Marchal G, Decsi T, Cruz M, Szabo E, Demmelmair H, et al. Spanish pregnant women's plasma phospholipids LC‐PUFAs concentrations and its influence on their newborns. Journal of Pediatric Gastroenterology and Nutrition 2004;39(Suppl 1):S11.
    1. Decsi T, Campoy C, Koletzko B. Effect of n‐3 polyunsaturated fatty acid supplementation in pregnancy: the nuheal trial. Advances in Experimental Medicine & Biology 2005;569:109‐13. - PubMed
    1. Demmelmair H, Klingler M, Campoy C, Decsi T, Koletzko B. Low eicosapentaenoic acid concentrations in fish oil supplements do not influence the arachidonic acid contents in placental lipids. Journal of Pediatric Gastroenterology and Nutrition 2004;39(Suppl 1):S11.
Edelstein 1968 {published data only}
    1. Edelstein T, Stevens K, Baumslag N, Metz J. Folic acid and vitamin B12 supplementation during pregnancy in a population subsisting on a sub‐optimal diet. Journal of Obstetrics and Gynaecology of the British Commonwealth 1968;75:133‐7. - PubMed
Fleming 1968 {published data only}
    1. Fleming AF, Hendrickse JP, Allan NC. The prevention of megaloblastic anaemia in pregnancy in Nigeria. Journal of Obstetrics and Gynaecology of the British Commonwealth 1968;75(4):425‐32. - PubMed
Fletcher 1971 {published data only}
    1. Fletcher J, Gurr A, Fellingham FR, Prankerd TAJ, Brant HA, Menzies DN. The value of folic acid supplements in pregnancy. Journal of Obstetrics and Gynaecology of the British Empire 1971;78:781‐5. - PubMed
Giles 1971 {published data only}
    1. Giles PF, Harcourt AG, Whiteside MG. The effect of prescribing folic acid during pregnancy on birthweight and duration of pregnancy. A double blind trial. Medical Journal of Australia 1971;2:17‐21. - PubMed
Harrison 1985 {published data only}
    1. Fleming AF, Ghatoura GBS, Harrison KA, Briggs ND, Dunn DT. The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria. Annals of Tropical Medicine and Parasitology 1986;80:211‐33. - PubMed
    1. Fleming AF, Ludwig H, Thomsen K. Anaemia in pregnancy in the Guinea Savanna of Nigeria. Gynecology and Obstetrics. Berlin: Springer‐Verlag, 1986:122‐4.
    1. Harrison KA, Fleming AF, Briggs ND, Rossiter CE. Child‐bearing, health and social priorities: a survey of 22,774 consecutive hospital births in Zaria, Northern Nigeria. 5. Growth during pregnancy in Nigerian teenage primigravidae. British Journal of Obstetrics and Gynaecology 1985;92(5):32‐9. - PubMed
Hibbard 1969a {published data only}
    1. Hibbard BM, Hibbard ED. The prophylaxis of folate deficiency in pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1969;48:339‐48. - PubMed
Iyengar 1975 {published data only}
    1. Iyengar L. Effect of folic acid supplementation on birth weight of infants. American Journal of Obstetrics and Gynaecology 1974;122:332‐6. - PubMed
    1. Iyengar L. Folic acid requirements of Indian pregnant women. American Journal of Obstetrics and Gynecology 1971;111(1):13‐6. - PubMed
    1. Iyengar L, Apte SV. Prophylaxis of anemia in pregnancy. American Journal of Clinical Nutrition 1970;23(6):725‐30. - PubMed
Lira 1989 {published data only}
    1. Lira P, Barrena N, Foradori A, Gormaz G, Grebe G. Folate deficiency in pregnancy: effect of supplementary folic acid [Deficienca de folatos en el embarazo: efecto de una suplementacion con acido folico]. Sangre 1989;34(1):24‐7. - PubMed
Menon 1962 {published data only}
    1. Menon MKK, Rajan L. Prophylaxis of anaemia in pregnancy. Journal of Obstetrics and Gynaecology of India 1962;12:382‐9.
Metz 1965 {published data only}
    1. Metz J, Festenstein H, Welch P. Effect of folic acid and vitamin B12 supplementation on test of folate and Vitamin B12 nutrition in pregnancy. American Journal of Clinical Nutrition 1965;16:472‐9. - PubMed
Pack 1980 {published data only}
    1. Pack ARC, Thomson ME. Effects of folic acid (FA) supplementation on gingivitis in pregnancy. Journal of Dental Research 1980;59(D1):1777.
    1. Pack ARC, Thomson ME. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. Journal of Clinical Periodontology 1980;7:402‐14. - PubMed
Rae 1970 {published data only}
    1. Rae PG, Robb PM. Megaloblastic anaemia of pregnancy: a clinical and laboratory study with particular reference to the total and labile serum folate levels. Journal of Clinical Pathology 1970;23:379‐91. - PMC - PubMed
Rolschau 1979 {published data only}
    1. Rolschau J, Date J, Kristoffersen K. Folic acid supplement and intrauterine growth. Acta Obstetricia et Gynecologica Scandinavica 1979;58:343‐6. - PubMed
Roth 1980 {published data only}
    1. Roth F, Mauracher E. Folic acid treatment during pregnancy [Folsauresubstitution bei schwangeren]. Geburtshilfe und Frauenheilkunde 1980;40:253‐8. - PubMed
Srisupandit 1983 {published data only}
    1. Srisupandit S, Pootrakul P, Areekul S, Neungton S, Mokkaves J, Kiriwat O, et al. A prophylactic supplementation of iron and folate in pregnancy. Southeast Asian Journal of Tropical Medicine and Public Health 1983;14:317‐23. - PubMed
Tchernia 1982 {published and unpublished data}
    1. Tchernia G, Blot I, Rey A, Kaltwasser JP, Zittoun J, Papiernik E. Maternal folate status, birthweight and gestational age. Developmental Pharmacology Therapeutics 1982;4:58‐65. - PubMed
Trigg 1976 {published data only}
    1. Trigg KH, Rendall EJC, Johnson A, Fellingham FR, Prankerd TAJ. Folate supplements during pregnancy. Journal of the Royal College of General Practitioners 1976;26:228‐30. - PMC - PubMed
Weil 1977 {published data only}
    1. Weil A, Mauracher E. Folic acid and pregnancy, a real problem? [Acide folique et gravidité, problème réel?]. Schweizer Medizinische Wochenschrift 1977;107:1943‐7. - PubMed
Willoughby 1967 {published data only}
    1. Willoughby ML. An investigation of folic acid requirements in pregnancy. II. British Journal of Hematology 1967;13(4):503‐9. - PubMed
    1. Willoughby ML, Jewell FJ. Investigation of folic acid requirements in pregnancy. British Medical Journal 1966;2(5529):1568‐71. - PMC - PubMed
    1. Willoughby MLN, Jewell FG. Folate status throughout pregnancy and in postpartum period. British Medical Journal 1968;4:356‐60. - PMC - PubMed

References to studies excluded from this review

Bjerre 1967 {published data only}
    1. Bjerre B. Study of the haematological effect of prophylactic folic acid medicamentation in pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1967;46(4):71‐85. - PubMed
Colman 1974 {published data only}
    1. Colman N, Barker M, Green R, Metz J. Prevention of folate deficiency in pregnancy by food fortification. American Journal Clinical Nutrition 1974;27:339‐44. - PubMed
Colman 1975 {published data only}
    1. Colman N, Larsen JV, Barker M, Barker EA, Green R, Metz J. Prevention of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid. American Journal of Clinical Nutrition 1975;28:465‐70. - PubMed
Ellison 2004 {published data only}
    1. Ellison J, Clark P, Walker ID, Greer IA. Effect of supplementation with folic acid throughout pregnancy on plasma homocysteine concentration. Thrombosis Research 2004;114:25‐7. - PubMed
Giles 1960 {published data only}
    1. Giles C, Burton H. Observations on prevention and diagnosis of anaemia in pregnancy. British Medical Journal 1960;2:636‐40. - PMC - PubMed
Gregory 2001 {published data only}
    1. Gregory JF 3rd, Caudill MA, Opalko FJ, Bailey LB. Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable‐isotopic labeling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools. Journal of Nutrition 2001;131(7):1928‐37. - PubMed
Hague 1998 {published data only}
    1. Hague B, Crowther C, Robinson J, Dekker G, Odendaal H. Prevention of recurrent pre‐eclampsia by folic acid supplementation in women with hyperhomocysteinaemia: proposal for a randomized trial. Netherlands Journal of Medicine 1998;52:S24.
    1. Hague B, Dekker G, Crowther C, Robinson J, Odendaal H. The HOPE (hyperhomocysteinaemia in pre‐eclampsia) trial: prevention of recurrent pre‐eclampsia by folic acid supplementation in women with hyperhomocysteinemia. Hypertension in Pregnancy 2000;19(Suppl 1):Abstract no P10.
Hamilton 1973 {published data only}
    1. Hamilton PJS, Gebbie DAM. Antenatal clinics as trial units in evaluating treatment of anaemia in pregnancy. The use and abuse of drugs and chemicals in Tropical Africa. Proceedings of the 1973 Annual Scientific Conference of the East African Medical Research Council. Nairobi, Kenya.: Nairobi: East African Literature Bureau, 1973:463‐6.
Hekmatdoost 2011 {published data only}
    1. Hekmatdoost A. Comparison of the effect of folic acid and 5‐methyltetrahydrofolate (5MTHF) on serum folate and homocysteine levels, and abortion rates in women suffering from recurrent abortion. IRCT Iranian Registry of Clinical Trials (www.irct.ir) (accessed 8 July 2011).
Hibbard 1969 {published data only}
    1. Hibbard BM, Hibbard ED. The treatment of folate deficiency in pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1969;48:349‐56. - PubMed
Khanna 1977 {published data only}
    1. Khanna S, Dube B, Kumar S. Anaemia of pregnancy in northern India. Nature and therapeutic follow‐up. Tropical & Geographical Medicine 1977;29(1):24‐8. - PubMed
Klinger 2006 {published data only}
    1. Klingler M, Blaschitz A, Campoy C, Cano A, Molloy AM, Scott JM, et al. The effect of docosahexaenoic avid and folic acid supplementation on placental apoptosis and proliferation. British Journal of Nutrition 2006;96(1):182‐90. - PubMed
Kristoffersen 1979 {published data only}
    1. Kristoffersen K, Rolschau J, Date JV, Honore E. The influence of folic acid supplement on intrauterine growth [abstract]. 9th World Congress of Gynecology and Obstetrics;Tokyo, Japan; 1979 October 26‐31. 1979:242.
Ma 2008 {published data only}
    1. Ma AG, Schouten EG, Zhang FZ, Kok FJ, Yang F, Jiang DC, et al. Retinol and riboflavin supplementation decreases the prevalence of anaemia in Chinese pregnant women taking iron and folic acid supplements. Journal of Nutrition 2008;138(10):1946‐50. - PubMed
Manizheh 2009 {published data only}
    1. Manizheh SM, Mandana S, Hassan A, Amir GH, Mahlisha KS, Morteza G. Comparison study on the effect of prenatal administration of high dose and low dose folic acid. Saudi Medical Journal 2009;30(1):88‐97. - PubMed
Melli 2008 {published data only}
    1. Melli MS, Shojaiee M, Sheshvan MK. Prenatal administration of high dose and low dose of folic acid on maternal plasma homocysteine concentration and its relationship to the development of preeclampsia. Journal of Maternal‐Fetal and Neonatal Medicine 2008;21(Suppl 1):82.
Ouma 2006 {published data only}
    1. Ouma P, Parise ME, Hamel MJ, ter Kuile FO, Otieno K, Ayisi JG, et al. A randomised controlled trial of folate supplementation when treating malaria in pregnancy with sulfadoxine‐pyrimethamine. PLoS Clinical Trials 2006;1(6):e28. - PMC - PubMed
    1. Eijk AM, Ouma PO, Williamson J, ter Kuile FO, Parise M, Otieno K, et al. Plasma folate level and high‐dose folate supplementation predict sulfadoxine‐primethamine treatment failure in pregnant women in Western Kenya who have uncomplicated malaria. Journal of Infectious Diseases 2008;198(10):1550‐3. - PubMed
Polatti 1992 {published data only}
    1. Polatti F, Perotti F, Nappi R, Prandi P. Calcium folinate in pregnancy: therapeutic efficacy [Calcio folinato in gravidanza]. Minerva Ginecologica 1992;44:33‐7. - PubMed
Taylor 1979 {published data only}
    1. Taylor DJ, Lind T. Red cell mass during and after normal delivery. British Journal of Obstetrics and Gynaecology 1979;86:364‐70. - PubMed
Taylor 1981 {published data only}
    1. Taylor DJ, Lind T. Pueperal haematological indices. British Journal of Obstetrics and Gynaecology 1981;88:601‐6. - PubMed
Tchernia 1982a {published data only}
    1. Tchernia G, Blot I, Rey A, Papiernik E. Maternal iron and folate deficiencies. Incidence on the newborn. Annales de Pediatrie 1982;29:276‐80. - PubMed
Thomson 1982 {published data only}
    1. Thomson ME, Pack ARC. Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. Journal of Clinical Periodontology 1982;9:275‐80. - PubMed
    1. Thomson ME, Pack ARC. Systemic folic acid (F.A.) supplementation and effects of pregnancy gingivitis. Journal of Dental Research 1981;60:1072.
Ulrich 1999 {published data only}
    1. Ulrich M, Kristoffersen K, Rolschau J, Grinsted P, Schaumburg E, Foged N. The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part II. Congenital anomalies. A randomised study. European Journal of Obstetrics & Gynecology and Reproductive Biology 1999;87(2):111‐3. - PubMed
Wang 2012 {published data only}
    1. Wang W, Yan H, Zeng L, Cheng Y, Wang D, Li Q. No effect of maternal micronutrient supplementation on early childhood growth in rural western China: 30 month follow‐up evaluation of a double blind, cluster randomized controlled trial. European Journal of Clinical Nutrition 2012;66(2):261‐8. - PubMed
Zeng 2008 {published data only}
    1. Zeng L, Dibley MJ, Cheng Y, Dang S, Chang S, Kong L, et al. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ 2008;337:a2001. - PMC - PubMed
    1. Zeng L, Yan H, Cheng Y, Dang S, Dibley MJ. Adherence and costs of micronutrient supplementation in pregnancy in a double‐blind, randomized, controlled trial in rural western China. Food and Nutrition Bulletin 2009;30(4):S480‐7. - PubMed

References to ongoing studies

Wen 2012 {published data only}
    1. Wen SW. Effect of folic acid supplementation in pregnancy on pre‐eclampsia ‐ folic acid clinical trial (FACT). Current Controlled Trials (http://www.current‐trials.com) (accessed 8 July 2011).
    1. Wen SW, Champagne J, Rennicks R, Walker M. Effect of folic acid supplementation in pregnancy on preeclampsia ‐ Folic acid clinical trial (FACT). Pregnancy Hypertension 2012;2(3):180. - PubMed
    1. Wen SW, Walker M. Effect of folic acid supplementation in pregnancy on preeclampsia. Pregnancy Hypertension 2010;1(Suppl 1):S28. - PubMed

Additional references

Açkurt 1995
    1. Açkurt F, Wetherilt H, Löker M, Hacibekiro M. Biochemical assessment of nutritional status in pre‐ and post‐natal Turkish women and outcome of pregnancy. European Journal of Clinical Nutrition 1995;49:613‐22. - PubMed
Bailey 1995
    1. Bailey LB. Folate requirements and dietary recommendations. In: Bailey LB editor(s). Folate in Health and Disease. New York: Marcel Dekker, 1995:123‐52.
Bates 1986
    1. Bates CJ, Fuller NJ, Prentice AM. Folate status during pregnancy and lactation in a West African rural community. Human Nutrition. Clinical Nutrition 1986;40:3‐13. - PubMed
Botto 1996
    1. Botto LD, Khoury MJ, Mulinare J, Erickson JD. Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population based, case‐control study. Pediatrics 1996;98(5):911‐7. - PubMed
Bruinse 1995
    1. Bruinse HW, Berg H. Changes of some vitamin levels during and after normal pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology 1995;61:31‐7. - PubMed
Bukowski 2009
    1. Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GDV, et al. Preconception folate supplementation and the risk of spontaneous preterm birth: prospective cohort study. PLoS Medicine 2009;6(5):e1000061. - PMC - PubMed
Caudill 1998
    1. Caudill MA, Gregory JF III, Hutson AD, Bailey LB. Folate catabolism in pregnant and nonpregnant women with controlled folate intakes. Journal of Nutrition 1998;128(2):204‐8. - PubMed
Chanarin 1969
    1. Chanarin I. The Megaloblastic Anemias. London, United Kingdom: Blackwell Scientific, 1969:786‐829.
Charles 2005b
    1. Charles DHM, Ness AR, Campbell D, Smith GD, Whitely E, Hall MH. Folic acid supplements in pregnancy and birth outcome: re‐analysis of a large randomised controlled trial and update of Cochrane review. Pediatric and Perinatal Epidemiology 2005;19:112‐24. - PubMed
Czeizel 1992
    1. Czeizel AE, Dudas I. Prevention of the first occurrence of neural‐tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 1992;327(26):1832‐5. - PubMed
Czeizel 1993
    1. Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 1993;306(6893):1645‐8. - PMC - PubMed
Czeizel 1996
    1. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. American Journal of Medical Genetics 1996;62(2):179‐83. - PubMed
De Benoist 2008
    1. Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutrition Bulletin 2008;29(Suppl 2):S238‐S244. - PubMed
De‐Regil 2010
    1. De‐Regil LM, Fernández‐Gaxiola AC, Dowswell T, Peña‐Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database of Systematic Reviews 2010, Issue 10. [DOI: 10.1002/14651858.CD007950.pub2] - DOI - PMC - PubMed
Dietary Ref 1998
    1. Anonymous. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic acid, Biotin and Choline. Institute of Medicine, 1998. - PubMed
Fleming 1972
    1. Fleming AF. Urinary excretion of folate in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1972;79:916‐20. - PubMed
Food and Nutrition Board 1970
    1. Food, Nutrition Board. National Research Council. Maternal Nutrition and the Course of Pregnancy. Washington, DC: National Academy of Sciences, 1970.
Food and Nutrition Board 1998
    1. Food, Nutrition Board. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington, DC: National Academy Press, 1998. - PubMed
Goldenberg 1992
    1. Goldenberg RL, Tamura T, Cliver SP, Cutter GR, Hoffman HJ, Copper RL. Serum folate and fetal growth retardation: a matter of compliance?. Obstetrics and Gynecology 1992;79:719‐22. - PubMed
Green 1995
    1. Green R, Jacobsen DW. Clinical implications of hyperhomocysteinemia. In: Bailey LB editor(s). Folate in Health and Disease. Newyork (NY): Marcel Dekker, 1995:75‐122.
Gregory 2001b
    1. Gregory JF III, Caudill MA, Opalko J, Bailey LB. Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable‐isotopic labelling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools. Journal of Nutrition 2001;131:1928‐37. - PubMed
Haider 2006
    1. Haider BA, Bhutta ZA. Multiple‐micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD004905.pub2] - DOI - PubMed
Herbert 1997
    1. Herbert V, Bigaoutte J. Call for endorsement of a petition to the Food and Drug Administration to always add vitamin B‐12 to any folate fortification or supplement. American Journal of Clinical Nutrition 1997;65(2):572‐3. - PubMed
Higgins 2000
    1. Higgins JR, Quinlivan EP, McPartlin J, Scott JM, Weir DG, Darling MRN. The relationship between increased folate catabolism and the increased requirement for folate in pregnancy. BJOG: an international journal of obstetrics and gynaecology 2000;107:1149‐54. - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Institute of Medicine 2000
    1. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington, DC: National Academy Press, 2000:196‐305. - PubMed
Krishnaswamy 2001
    1. Krishnaswamy K, Nair KM. Importance of folate in human nutrition. British Journal of Nutrition 2001;85:S115‐S124. - PubMed
Landon 1971
    1. Landon MJ, Hytten FE. The excretion of folate in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 1971;78:769‐75. - PubMed
Lawson 1988
    1. Lawson JB. Anaemia in pregnancy. In: Lawson JB, Stewart DB editor(s). Obstetrics and Gynaecology in the Tropics and Developing Countries. London: Edward Arnold, 1988:76‐8.
Li 1995
    1. Li DK, Daling JR, Mueller BA, Hickik DE, Fantel AG, Weiss NS. Periconceptional multivitamin use in relation to the risk of congenital urinary tract anomalies. Epidemiology 1995;6(3):212‐8. - PubMed
Makedos 2007
    1. Makedos G, Papanicolaou A, Hitoglou A, Kalogiannidis I, Makedos A, Vrazioti V, et al. Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia. Archives of Gynecology and Obstetrics 2007;275(2):121–4. - PubMed
McPartlin 1993
    1. McPartlin J, Halligan A, Scott JM, Darling M, Weir DG. Accelerated folate breakdown in pregnancy. Lancet 1993;341(8838):148‐9. - PubMed
Morrison 1998
    1. Morrison K, Papapetrou C, Hol FA, Mariman EC, Lynch SA, Burn J, et al. Susceptibility to spina bifida; an association study of five candidate genes. Annals of Human Genetics 1998;62(5):379‐96. - PubMed
MRC 1991
    1. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338(8760):131‐7. - PubMed
Neggers 1997
    1. Neggers YH, Goldenberg RL, Tamura T, Cliver SP, Hoffman HJ. The relationship between maternal dietary intake and infant birthweight. Acta Obstetricia et Gynecologica Scandinavica 1997;165:71‐5. - PubMed
NICE 2008
    1. National Institute for Health and Clinical Excellence. NICE public health guidance 11: Improving the nutrition of pregnant and breastfeeding mothers and children in low‐income households. London: NICE, 2011 July.
Patrick 2004
    1. Patrick TE, Powers RW, Daftary AR, Ness RB, Roberts JM. Homocysteine and folic acid are inversely related in black women with preeclampsia. Hypertension 2004;43(6):1279–82. - PubMed
Pena‐Rosas 2006
    1. Pena‐Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid for women during pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD004736.pub2] - DOI - PubMed
Refsum 2008
    1. Refsum H, Smith AD. Are we ready for mandatory fortification withvitamin B‐12?. American Journal of Clinical Nutrition 2008;88(2):253–4. - PubMed
RevMan 2011 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Rush 1994
    1. Rush D. Periconceptional folate and neural tube defect. American Journal of Clinical Nutrition 1994;59(Suppl 1):511S‐515S. - PubMed
Scholl 2000
    1. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. American Journal of Clinical Nutrition 2000;71:1295‐303. - PubMed
Selhub 1993
    1. Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693‐8. - PubMed
Shaw 1995
    1. Shaw GM, Lammer EJ, Wasserman CR, O'Malley CD, Tolarova MM. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995;346(8972):393‐6. - PubMed
Smith 1983
    1. Smith AM, Picciano MF, Deering RH. Folate supplementation during lactation: maternal folate status, human milk folate content, and their relationship to infant folate status. Journal of Pediatric Gastroenterology and Nutrition 1983;2:622‐8. - PubMed
Smits 2001
    1. Smits LJM, Essed GGM. Short interpregnancy intervals and unfavourable pregnancy outcome: role of folate depletion. Lancet 2001;358:2074‐7. - PubMed
Tamura 1992
    1. Tamura T, Goldenberg RL, Freeberg LE, Cliver SP, Cutter GR, Hoffman HJ. Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. American Journal of Clinical Nutrition 1992;56:365‐70. - PubMed
Tamura 2006
    1. Tamura T, Picciano MF. Folate and human reproduction. American Journal of Clinical Nutrition 2006;83(5):93‐1016. - PubMed
Willoughby 1968
    1. Willoughby MLN. Folate status throughout pregnancy and in post partum period. British Medical Journal 1968;4:356‐60. - PMC - PubMed

References to other published versions of this review

Mahomed 1995
    1. Mahomed K. Routine folate supplementation in pregnancy. [revised 28 April 1993]. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, Crowther C (eds.) Pregnancy and Childbirth Module. In: The Cochrane Pregnancy and Childbirth Database [database on disk and CDROM]. The Cochrane Collaboration; Issue 2, Oxford: Update Software; 1995.
Mahomed 1997
    1. Mahomed K. Folate supplementation in pregnancy. Cochrane Database of Systematic Reviews 1996, Issue 3. [DOI: 10.1002/14651858.CD000183.pub2] - DOI - PubMed

MeSH terms