Possible Association of Folic Acid Supplementation During Pregnancy With Reduction of Preterm Birth: A Population-Based Study EDITORIAL COMMENT

Semmelweis University, Budapeŝto, Budapest, Hungary
European journal of obstetrics, gynecology, and reproductive biology (Impact Factor: 1.7). 11/2009; 148(2):135-40. DOI: 10.1016/j.ejogrb.2009.10.016
Source: PubMed


Periconceptional folic acid or multivitamin supplementation is recommended for prospective pregnant women to prevent neural-tube defects. The question is whether it is worth continuing these supplementations after the first trimester of pregnancy or not. Thus the possible fetal growth promoting and/or preterm birth reducing effect of vitamin supplements in the second and mainly in the third trimester was studied.
Comparison of birth outcomes of singletons born to primiparous pregnant women with prospectively and medically recorded vitamin supplement in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996 contained 6293, 169, and 311 primiparae with folic acid alone, multivitamins and folic acid+multivitamin supplementation, respectively, and their data were compared to the data of 7319 pregnant women without folic acid and folic acid-containing multivitamin supplementation as reference.
Mean gestational age was 0.3 week longer and mean birth weight was by 37 g higher in the group of folic acid alone, than in the reference group (39.2 weeks; 3216 g). The rate of preterm births (7.6%) was significantly lower compared with the reference sample (11.8%), but the rate of low birth weight newborns did not show significant reduction. Folic acid alone in the third trimester associated with 0.6 week longer gestational age and a more significant reduction in the rate of preterm births (4.8%).
Minor increase in mean birth weight after high dose of folic acid supplementation during pregnancy would not be expected to result in too large babies; however, the significant reduction in the rate of preterm births may have great public health benefit.

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    • "39.8 weeks and 4.9%), followed by the 3 rd trimester alone (39.5 weeks and 7.6%) [33] "
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    ABSTRACT: Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.
    Journal of Perinatal Medicine 03/2015; DOI:10.1515/jpm-2014-0346 · 1.36 Impact Factor
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    • "The study of Papadopoulou [63] suggests a decrease of PTB in women supplemented with 5 mg of FA in early-midpregnancy. This result is confirmed also in a large cohort (38,151 women) [64] that used a similar dose of FA in the periconceptional period, but not in the “Generation R study” [65]. "
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    ABSTRACT: Introduction: Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. Aim of the study: The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. Materials and methods: We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. Results: The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB.
    03/2014; 2014(5):481914. DOI:10.1155/2014/481914
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    • "However, some recent observational studies have found that folic acid supplementation reduces the risk of PTD [20-22]. In some cases, this association was linked to pre-conceptional folic acid supplementation for 1 year or longer [21] or third-trimester folic acid supplementation [22], raising questions about extended supplementation schemes compared to the NTD prevention scheme. "
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    ABSTRACT: Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999--2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4--5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). The median total folate intake was 266 mug/d (interquartile range IQR 154--543) in the overall population and 540 mug/d (IQR 369--651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval 95% CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.
    BMC Pregnancy and Childbirth 08/2013; 13(1):160. DOI:10.1186/1471-2393-13-160 · 2.19 Impact Factor
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