Reduction of Incidence of Prematurity by Folic Acid Supplementation in Pregnancy

Baumslag, Naomi; Edelstein, T.; Metz, J.

doi:10.1136/bmj.1.5687.16

Cited by 155 publications

(62 citation statements)

References 20 publications

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“…In a landmark trial by Baumslag et al (25), 5 mg of daily FA supplementation after 28 wk was only effective in increasing the birthweight of Bantu women, whose daily folate intake was low compared to that of white women with frequent consumption of fruits and vegetables. In another trial conducted in Nepal, women were supplemented daily with 0.4 mg FA from about 11 wk to delivery.…”

Section: Discussionmentioning

confidence: 99%

Elevated Maternal Serum Folate in the Third Trimester and Reduced Fetal Growth: A Longitudinal Study

Takimoto¹,

Hayashi

Kusama

et al. 2011

J Nutr Sci Vitaminol

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SummaryThis study aimed to examine the association of fetal growth and elevated third trimester maternal serum folate due to folic acid (FA) supplement intake. Dietary intake, use of FA supplements, weight, and blood biomarkers of B-vitamins (serum folate, pyridoxal, vitamin B 12 , and plasma total homocysteine) were observed in 33 healthy pregnant women at the third trimester (average gestational age 35 wk). Birth outcomes were assessed through hospital birth records. Infant anthropometry and maternal blood biomarkers were followed up at 1 mo postpartum. Fourteen women were taking FA supplements at the third trimester. Dietary intake was similar among FA users and non-users, but serum folate and pyridoxal were significantly higher in users (11.6 Ϯ 6.7 vs. 6.1 Ϯ 3.2 ng/mL, and 13.8 Ϯ 21.7 vs. 3.2 Ϯ 1.4 ng/mL, respectively). Plasma total homocystein (tHcy) was higher in non-users compared to users, but not significantly. Nine FA users and eight non-users had low serum vitamin B 12 values ( Ͻ 203 pg/mL). Nine FA users and all non-users had low serum pyridoxal values ( Ͻ 7.0 ng/mL). Infant birthweight was significantly lower in users compared to non-users (2,894 Ϯ 318 vs. 3,154 Ϯ 230 g). At 1 mo postpartum, infant weight and length were similar between FA users and non-users, but infant weight gain was larger in users. Higher serum folate values due to FA use in the third trimester was related to reduced fetal size. Excess FA under low vitamin B 6 and B 12 status may affect fetal growth. Key Words pregnancy, folate, supplement use, birthweight Periconceptional folic acid (FA) supplements are currently recommended to women planning pregnancy, to avoid fetal neural tube defects (NTDs) ( 1 ) in Japan, and many other countries ( 2 ). Before its effect on NTD prevention was found, FA supplementation was previously known for its effect in preventing anemia in pregnancy ( 3 , 4 ). However, a number of recent studies have focused on other relations of folate to pregnancy health, such as pregnancy-induced hypertension ( 5-8 ), placental abruption ( 9 ), fetal growth restriction ( 10 ), and preterm birth ( 11 ), suggesting extended FA supplementation to reduce risks for these adverse pregnancy outcomes. While FA supplementation throughout pregnancy has been considered safe, concerns are arising on the long-term health effects of synthesized folate on infant health. Excess FA may induce changes to the genetic expression of the fetus, such as observed in animal experiments ( 12 , 13 ). This may pose lifetime changes to the health status of the offspring.Folate is an essential component in various metabolic processes, such as one-carbon transfer reactions including formate oxidation, amino acid metabolism and biosynthesis of thymidylate and purines ( 14 ). In regenerating methione from homocysteine, methionine synthase catalyzes the cobalamin-dependent transfer of a methyl group from 5-methyl-tetrahydrofolate. Homocysteine is also catalyzed into cysteine through the transsulfuration pathway, which involves cystathionine ␤ -synt...

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Section: Discussionmentioning

confidence: 99%

Elevated Maternal Serum Folate in the Third Trimester and Reduced Fetal Growth: A Longitudinal Study

Takimoto¹,

Hayashi

Kusama

et al. 2011

J Nutr Sci Vitaminol

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“…Although there is evidence that in animals a folate deficiency has detrimental consequences (59,60) the topic has been little considered in human subjects. There is a report that infants born to a mother with a severe folate deficiency during pregnancy showed delayed development (61) and that folic acid supplementation during pregnancy reduced the incidence of immaturity (62) . Tamura et al (63) associated the folate status of mothers during pregnancy and the cognitive development of their offspring.…”

Section: Folatementioning

confidence: 99%

Vitamins and neural and cognitive developmental outcomes in children

Benton

2011

Proc. Nutr. Soc.

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The role of vitamin status in the development of the brain and the subsequent functioning of the brain was considered. There are data with a range of vitamins, from animal studies and human studies in developing countries, suggesting that a clinical deficiency during the critical period when the brain is developing causes permanent damage. To date there is, however, with the exception of cases of clinical deficiency such as those that might be associated with a vegan diet, little evidence that variations in the diet of those living in industrialised countries have a lasting developmental influence. Similarly, later in life clinical deficiencies of various vitamins disrupt cognition although there is to date limited evidence that variations in the intake of single vitamins in industrialised societies influence functioning. It may well be, however, unreasonable to expect that vitamins examined in isolation will be associated with differences in cognitive functioning. The output of the brain reflects millions of metabolic processes, each potentially susceptible to any of a range of vitamins. A diet poor in one respect is likely to be poor in other respects as well. As such, the preliminary reports in double-blind placebo-controlled trials that aspects of cognition and behaviour respond to supplementation with multi-micronutrients may indicate the way forward.

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“…17 Intervention trials of prenatal folic acid supplementation have been conflicting, however. [18][19][20][21][22][23][24][25] Low serum folate is associated with impaired T-cell and neutrophil function and an increased prevalence of bacteriuria in pregnancy. [26][27][28] In a randomized trial in Nepal, folic acid supplementation decreased markers of inflammation during pregnancy, although this same study found no effect on PTB.…”

Section: Folatementioning

confidence: 99%

Maternal Micronutrient Status and Preterm Versus Term Birth for Black and White US Women

et al. 2012

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Objective. Micronutrient deficiencies are hypothesized to play a role in spontaneous preterm birth (PTB; <37 weeks of gestation) and possibly the racial disparity in rates of PTB between black and white women. Yet relatively few studies have addressed the role of micronutrient deficiencies in spontaneous PTB among black and white women in the United States. The purpose of this study was to investigate whether 25-hydroxy vitamin D (25-OH-D), folate, and omega-6/omega-3 fatty acid status are associated with spontaneous PTB among black and white women in the United States. Methods. Biospecimens and medical record data for this study were derived from a subsample of the 1547 women enrolled into the Nashville Birth Cohort during [2003][2004][2005][2006]. We randomly selected 80 nulliparous and primiparous women for whom stored plasma samples from the delivery admission were available and analyzed the stored plasma for 25-OH-D, folate, and total omega-6/omega-3 fatty acids. We used multivariate logistic regression to assess the odds of spontaneous PTB among women with 25-OH-D <20 ng/mL, folate <5 ug/L, and omega-6/omega-3 >15. Results. An omega-6/omega-3 ratio >15 was significantly associated with spontaneous PTB for white (adjusted odds ratio [aOR] 4.25, 95% confidence interval [CI] 1.25-14.49) but not black women (aOR 1.90, 95% CI: 0.69-5.40), whereas no significant relationships were observed for folate and 25-OH-D status and PTB for black or white women. Conclusion. Maternal plasma total omega-6/ omega-3 fatty acid ratio >15 at delivery was significantly associated with spontaneous PTB for white, but not black, women.

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Reduction of Incidence of Prematurity by Folic Acid Supplementation in Pregnancy

Cited by 155 publications

References 20 publications

Elevated Maternal Serum Folate in the Third Trimester and Reduced Fetal Growth: A Longitudinal Study

Elevated Maternal Serum Folate in the Third Trimester and Reduced Fetal Growth: A Longitudinal Study

Vitamins and neural and cognitive developmental outcomes in children

Maternal Micronutrient Status and Preterm Versus Term Birth for Black and White US Women

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