A prophylactic supplementation of iron and folate in pregnancy. The effect of prescribing folic acid during pregnancy on birth-weight and duration of pregnancy. A double-blind trial. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Preventive iron and folic acid therapy in pregnancy. Folic acid and vitamin B12 supplementation during pregnancy in a population subsisting on a suboptimal diet. The prophylaxis of folate deficiency in pregnancy. Folate supplements during pregnancy. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review. [Deficiency of folates in pregnancy: effect of supplementary folic acid]. Megaloblastic anaemia of pregnancy: a clinical and laboratory study with particular reference to the total and labile serum folate levels. A prophylactic trial of iron and folic acid supplements in pregnant Burmese women. The prevention of megaloblastic anaemia in pregnancy in Nigeria. Influence of routine administration of folic acid and iron during pregnancy. IRON DEFICIENCY AND ITS RELATION TO FOLIC-ACID STATUS IN PREGNANCY: RESULTS OF A CLINICAL TRIAL. [Substitution of folic acid in pregnancy (author's transl)]. Maternal folate status, birthweight and gestational age. [Folic acid deficiency in pregnant women in Switzerland]. Folic acid supplement and intrauterine growth. Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial. EFFECT OF FOLIC ACID AND VITAMIN B12 SUPPLEMENTATION ON TESTS OF FOLATE AND VITAMIN B12 NUTRITION IN PREGNANCY. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. [Folic acid and pregnancy, a real problem?].
The supplementation of iron and folic acid were studied in 567 pregnant women with 18 and 26 weeks of gestation. Sixty mg and 180 mg of iron were given daily to pregnant women of group I and group II respectively while 180 mg of iron and 5 mg folic acid were given to group III. The Hb values increased significantly in group II and III after supplementation for 1 1/2 months, however if supplementation was extended for 3 months, highly significant increase in Hb levels were observed in all these groups. These findings indicated that in supplementation for a shorter period, i.e. 1 1/2 months at least 180 mg of iron was needed, and only 60 mg of iron was sufficient to increase Hb levels for a supplementation of 3 months. Vitamin B12 deficiency was not detected in pregnant women both before and after supplementation with iron and iron plus folate for 3 months. It was suggested therefore that perhaps it was not necessary to supplement vitamin B12 to Thai pregnant women. In this study 15% of pregnant women had low serum folate with normal red cell folate level, and a greater number of women with low serum folate concentrations were observed after supplementation with iron alone for 3 months. However, increased serum folate and red cell folate levels after supplementation with 5 mg folic acid indicated that some pregnant women needed folate supplementation in preventing folic acid deficiency during pregnancy. nan Folic acid administered to pregnant Bantu, whose diet is low in folate, was associated with a significant reduction in the incidence of prematurity. No such effect could be demonstrated in White patients subsisting on an average Western diet. This suggests that folate deficiency may contribute to the "pregnancy wastage" in populations whose dietary folate intake is low, and is a further indication for folic acid supplementation during pregnancy in these groups. nan nan nan In a controlled, prospective trial, the effects of giving ferrous sulphate 50 mg daily to 76 pregnant women was compared with giving ferrous sulphate 50 mg daily plus folic acid 0.5 mg daily to 82 women in 12 general practices in South-east England.No differences in obstetric complications were found between the two groups, although the evidence of some of the listed complications may be too rare for detection in a sample of patients of this size. We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%.
                We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality.
                The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only.
                None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04).
                Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation. Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards. Higher folate needs are present during pregnancy, which may lead to tissular deficiency in the mother and to depleted newborn folate reserves. The aim of this work was to assess the prevalence of folate deficiency and to establish the rates of serum and red cell folate in two groups of mothers and newborn infants, one receiving only iron and the other iron and folate during pregnancy. The rates of serum and red cell folate found at the end of pregnancy were significantly higher in the group which received folate; however, the percentage of cases with tissular folate deficiency was low in both groups, with no significant difference (3.8% and 1.3%, respectively). These findings, along with the lack of effect of supplemental folate on erythropoiesis, pose some questions on the usefulness of supplemental folate during pregnancy in our country. It has been shown that the incidence of megaloblastic anaemia in a group of 463 randomly selected pregnant women receiving iron was 12 times as high as in a control group of 235 pregnant women receiving iron and folic acid. The incidence of all types of anaemia in the women receiving iron alone was more than three times the incidence in those having iron and folic acid. Some women who were not anaemic or who had normoblastic anaemia had serum folate levels in the same range as the women with megaloblastic anaemia, but none of the women with megaloblastic anaemia had high serum folate levels. The labile fraction of the serum folate was no more reliable than the total serum folate as a diagnostic criterion of megaloblastic erythropoiesis in the individual case. The blood group distribution in the women with megaloblastic anaemia was the same as in the general population. Babies born to mothers with megaloblastic anaemia tended to be smaller than the rest, although there was no difference in the placental weights. The significance of these findings is discussed. Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status. nan Haematological and folic acid status were assessed in 200 women in the 6th month of pregnancy. Folic acid deficiencies with no or little haematological impairment were found in one third of the cases, and their occurrence increased when the socioeconomic level was low. During the last trimester of pregnancy, the women were given either iron alone or iron and folic acid supplementation. In the mothers, the rise of folate values in serum and red blood cells, in the folic acid-supplemented group, had no obvious haematological consequences, showing that iron therapy alone can, in developed countries, prevent the anaemia in pregnancy. In the infants, there was no difference in the haematological indices, whatever the mothers' treatment had been. However, a significant difference appeared for the gestational age and, therefore, the height and weight. Folic acid supplementation during pregnancy increased its duration by virtually 1 week. nan nan nan nan The effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells. In this placebo controlled, randomised, double blind trial, pregnant women received from the 20th week of gestation onwards either 500 mg docosahexaenoic acid (DHA), 400 mg 5-methyl-tetra-hydro-folate (5-MTHF), or placebo, or a combination of 500 mg DHA and 400 mg 5-MTHF. The dietary supplements were well tolerated; the dropout rates did not differ significantly in the active arms of the study (10% to 19%) from that seen in the placebo group (13%). DHA supplementation resulted in significant enhancement of the contribution of DHA to maternal, placental and venous cord blood lipids. nan A double-blind study evaluated the effects of systemic and topical folate on gingival inflammation during the fourth and eighth months of pregnancy. Thirty women were randomly divided into three groups. Group A received placebo mouthwash and tablets; Group B; placebo mouthwash and 5 mg folate tablets; Group C: folate mouthwash and placebo tablets. Supplementation lasted for 14 days during months 4 and 8. Subjects took one tablet daily and rinsed twice daily for 1 min with the mouthwash. At the start and finish of each 14-day period, fasting serum and red cell folate levels were estimated and oral status assessed by a plaque index (P1I), a gingival index (GI), and gingival exudate flow meter (GEF). Subjects completed 1-week diet sheets which were analysed for dietary folate. All groups were similar in each parameter at the start. Correlation was demonstrated between GI and P1I, and between GI and GEF. GI tended to increase throughout pregnancy in all groups except Group C, when in the eighth month there was a highly significant improvement (0.001 less than P 0.01) despite no significant change in P1I. Although dietary intake of folate was significantly higher during the eighth month in Group C as compared with Groups A and B, (0.001 less than P less than 0.01), the folate mouthwash produced highly significantly improvement in gingival health in pregnancy. The efficacy of prophylactic treatment with ferrous sulfate (80 mg Fe++) and the combination of ferrous sulfate with folic acid (80 mg Fe++ and 350 microgram folic acid) were studied in a double blind trial in the 20th, and again in the 30th and 36th week of pregnancy (29 patients). At the beginning of the treatment (20th week) 29% of the patients showed a pathologically reduced serum folic acid level. Combined therapy has a favorable effect on the folic acid levels in the serum and red blood cells; this was confirmed statistically. At the end of pregnancy, 69% of the patients of the control group (ferrous sulfate) showed a pathologically reduced serum level and 23% a subnormal level in erythrocytes. These results unquestionably justify the prophylactic prescription of folic acid during pregnancy.
We found no conclusive evidence of benefit of folic acid supplementation during pregnancy on pregnancy outcomes.