The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria. Investigation of folic acid requirements in pregnancy. [Deficiency of folates in pregnancy: effect of supplementary folic acid]. Study of the Haematological Effect of Profylactic Folic Acid Medicamentation in Pregnancy Megaloblastic anaemia of pregnancy: a clinical and laboratory study with particular reference to the total and labile serum folate levels [Folic acid and pregnancy, a real problem?]. Reduction of Incidence of Prematurity by Folic Acid Supplementation in Pregnancy Folate Status Throughout Pregnancy and in Postpartum Period
Two hundred Hausa primigravidae at Zaria were divided into five groups in a r and omized double-blind trial of antenatal oral antimalarial prophylaxis , and haematinic supplements . Group 1 received no active treatment . Groups 2 to 5 were given chloroquine 600 mg base once , followed by proguanil 100 mg per day . In addition , group 3 received iron 60 mg daily , group 4 folic acid 1 mg daily , and group 5 iron plus folic acid .  Forty-five percent were anaemic ( haemoglobin ( Hb ) less than 11.0 g dl-1 ) at first attendance before 24 weeks of gestation , and malaria parasitaemia ( predominantly Plasmodium falciparum ) was seen in 27 % , of whom 60 % were anaemic . The mean Hb fell during pregnancy in group 1 , and seven patients in this group had to be removed from the trial and treated for severe anaemia ( packed cell volume ( PCV ) less than 0.26 ) . Only five patients in the other groups developed severe anaemia ( P = 0.006 ) , two of whom had malaria following failure to take treatment . Patients in group 1 had the lowest mean Hb at 28 and 36 weeks of gestation , and patients receiving antimalarials and iron ( groups 3 and 5 ) had the highest Hb at 28 weeks , but differences were not significant , possibly due to removal from the trial of patients with severe anaemia . Anaemia ( Hb less than 12.0 g dl-1 ) at six weeks after delivery was observed in 61 % of those not receiving active treatment ( group 1 ) , in 39 % of those protected against malaria but not receiving iron supplements ( groups 2 and 4 ) and in only 18 % of patients receiving both antimalarials and iron ( groups 3 and 5 ) . Folic acid had no significant effect on mean Hb .  Proguanil was confirmed to be a highly effective causal prophylaxis . Prevention of malaria , without folic acid supplements , reduced the frequency of megaloblastic erythropoiesis from 56 % to 25 % . Folic acid supplements abolished megaloblastosis , except in three patients who were apparently not taking the treatment prescribed . Red cell folate ( RCF ) concentrations were higher in subjects with malaria , probably due to intracellular synthesis by plasmodia . Infants of mothers not receiving antimalarials appeared to have an erythroid hyperplasia . Maternal folate supplements raised infants ' serum folate and RCF .  Fourteen per cent had low birth weight ( less than 2500 g ) , and the perinatal death rate was 11 % ; the greatest number were in group 1 , but not significantly . A regime is proposed for the prevention of malaria , iron deficiency , folate deficiency and anaemia in pregnancy in the guinea savanna of Nigeria Bertino , J. R. , Ward , J. , Sartorelli , A. C. , and Silber , R. ( 1965 ) . 7 . clin . Invest . , 44 , 1028 . Bothwell , T. H. , Hurtardo , A. V. , Donohue , D. M. , and Finch , C. A. ( 1957 ) . Blood , 12 , 409 . Callender , S. T. , and Malpas , J. S. ( 1963 ) . Brit . med . 7 . , 2 , 1516 . Cockburn , F. , Sherman , J. D. , Ingall , D. , and Klein , R. ( 1965 ) . Proc . Soc . exp . Biol . ( N.Y. ) , 118 , 238 . Conrad , M. E. , Berman , A. , and Crosby , W. H. ( 1962 ) . Gastroenterology , 43 , 385 . Dacie , J. V. , and Lewis , S. M. ( 1963 ) . Practical Haematology , 3rd ed . London . Davis , A. E. , and Badenoch , J. ( 1962 ) . Lancet , 2 , 6 . Finch , C. A. , Coleman , D. H. , Motulsky , A. G. , Donohue , D. M. , and Reiff , R. H. ( 1956 ) . Blood , 11 , 807 . Herbert , V. ( 1963 ) . Amer . 7 . clan . Nutr . , 12 , 17 . Gottlieb , C. W. , and Altschule , M. D. ( 1965 ) . Lancet , 2 , 1052 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 Our interest in the problem of folic acid and pregnancy was aroused by the work of Hibbard and Hibbard : “ Aetiological factors in abruptio placentae ” 1963 ( 12 ) . Though the frequency of abruptio placentae at our department is by no means so high as that at Millroad Maternity Hospital , Liverpool , the complication is serious because of its foetal mortality . We therefore thought it advisable to try folic acid prophylaxis during pregnancy in an attempt to decrease the frequency of abruptio placentae . Later investigations ( 14 , 20 ) have , however , shown that if folic acid treatment is not started until pregnancy has been diagnosed , it will hardly be able to reduce the frequency of abruptio placentae and abortion . In Great Britain megaloblastic anaemia due to folic acid deficiency is common during pregnancy ( 4 , 5 , 6 , 7 , 8 , 13 , 15 , 16 , IS ) , while in Sweden only a few cases have been reported . This discrepancy can be explained only partly by differences in interest in the diagnosis and diagnostic facilities available . In a thoroughly examined series Hansen found megaloblastic anaemia in less than 0.1 % of all pregnant women during a 3 1/2-year-period in Gothenburg ( 9 ) . A poor composition of the diet was thought to be a main causal factor of folic acid deficiency in the series reported from It has been shown that the incidence of megaloblastic anaemia in a group of 463 r and omly 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 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 un question ably justify the prophylactic prescription of folic acid during pregnancy 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 population s whose dietary folate intake is low , and is a further indication for folic acid supplementation during pregnancy in these groups The serial trends of the  whole blood folate level  in two groups of patients have been followed throughout pregnancy and up to six weeks postpartum . In those  receiving iron alone the whole blood folate remained normal until the test at six weeks after delivery , at which time over half were in the deficient range . There appears to be a delay before this test reflects the current folate status when this changes rapidly . In those receiving iron plus 330 μg . of folic acid a day the results at this time were close to those at the beginning of pregnancy . Subnormal whole blood folate , red cell folate , and serum folate values occurred close to term in patients receiving iron alone , but were not found in those also receiving folic acid .  Megaloblastic changes occurred at term in three patients receiving iron alone in whom the whole blood folate had repeatedly been low in early pregnancy . The observations are consistent with the previous suggestion that 300 μg . of folic acid daily is a suitable supplement to prevent deficiency in late pregnancy and the puerperium
BACKGROUND Folate depletion may result in anaemia during pregnancy .
OBJECTIVES The objective of this review was to assess the effects of folate supplementation in pregnancy on haematological and biochemical parameters and measures of pregnancy outcome .
This review did not address the role of periconceptual folate supplementation to diminish the risk of fetal malformation .