human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Efforts to determine the impact of prenatal multivitamin supplementation on birth outcome have been carried out in several developing countries . A review of factors that would impact the effectiveness of prenatal supplementation under normal field conditions is currently lacking and will be required for exp and ed supplementation programs . An efficacy trial of a multiple micronutrient supplement for pregnant women was conducted in rural western China , and additional information on side effects , rates of adherence , program inputs , and cost was also gathered . Objectives To examine reports of side effects and rates of adherence to prenatal multiple micronutrient supplementation in comparison with supplementation with folic acid and with iron – folic acid , and to describe inputs and costs associated with prenatal supplementation in China . Methods A cluster-r and omized , double-blind , controlled trial was conducted in two rural counties in northwest China . All pregnant women in villages were r and omly assigned to take daily supplements of folic acid , iron – folic acid , or a recommended daily allowance of 15 vitamins and minerals from enrollment until delivery . Information was collected from the women on side effects and adherence . Program inputs and costs of supplementation were tracked . Descriptive statistics were used for the analysis . The biological effectiveness of prenatal multiple micronutrient supplements is reported elsewhere . Results Less than 4 % of women withdrew from the study because of side effects . Adherence to supplementation was high : the supplements were consumed on more than 90 % of the days on which they were available for consumption . The mean number of supplements consumed was high at 165 capsules , and about 40 % consumed the recommended 180 supplements during pregnancy . Conclusions High adherence to a prenatal supplement schedule can be achieved when mothers have frequent contact with trained health workers and a reliable supply of supplements 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 In a controlled , prospect i ve 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 practice s in South-east Engl and .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 UNLABELLED Sulfadoxine-pyrimethamine ( SP ) inhibits folate metabolism by the malaria parasite . We investigated the association between folate levels and SP failure in pregnant women . Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed . Plasma folate levels were determined at enrollment and at day 7 . High baseline folate levels , high parasite densities , and age < 20 years were risk factors for SP failure . High-dose ( 5 mg daily ) folate supplementation or high folate levels at day 7 were independent risk factors . Therefore , pregnant women receiving SP should receive low-/moderate-dose folate supplementation . TRIAL REGISTRATION http://www . clinical trials.gov identifier : NCT00130065 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 The hypothesis was tested that the additional dietary uptake of n-3 fatty acids , in particular of DHA and 5-methyltetrahydrofolate ( 5-MTHF ) , during the second half of pregnancy would influence proliferation and apoptosis in the full-term human placenta . The diets of pregnant women from Spain ( n 55 ) were supplemented with modified fish oil and /or 5-MTHF or placebo , and assigned in a r and om , double-blind manner to one of the four groups . Immunohistochemistry and immunoblotting were used to detect placental proliferation and apoptosis with monoclonal antibodies for key proteins that reflected the extent of both processes : proliferation cell nuclear antigen ( PCNA ) , p53 , cytokeratin 18 neoepitope . The PCNA level in the fish oil/5-MTHF-treated group was higher by 66 % ( P < 0.05 ) than that of the placebo group , whereas the levels of p53 and cytokeratin 18 neoepitope were unaffected by treatment . PCNA expression was altered only in the trophoblast compartment ( placebo 11.1 ( se 0.5 ) % v. combination 21.5 ( se 1.2 ) % ; P < 0.05 ) , whereas the proportion of nuclei stained in endothelial and other stromal cells was similar in the placebo and combined treatment groups . No correlation was found between fish oil or 5-MTHF supplementation and the levels of the proteins . The present data suggest that supplementation with fish oil and /or 5-MTHF had no effect on the parameters reflecting placental proliferation and apoptosis . A defined combination of DHA and 5-MTHF may , however , affect placental proliferation Iron deficiency is one of the main causes of anemia during pregnancy , although other micronutrient deficiencies may play a role . We examined the effects of daily antenatal and postnatal supplementation with four combinations of micronutrients on  maternal hematologic indicators  in a double-masked r and omized controlled community trial . Communities , called sectors , were r and omly assigned to supplementation with folic acid ( 400 microg ) , folic acid plus iron ( 60 mg ) , folic acid plus iron and zinc ( 30 mg ) and folic acid plus iron , zinc and 11 other micronutrients , each at the approximate recommended daily allowance for pregnancy all given with vitamin A as retinol acetate ( 1000 microg retinol equivalent ) , or vitamin A alone as the control group .  Hemoglobin ( Hb ) and indicators of iron status were assessed at baseline and at 32 wk of gestation . At 6-wk postpartum , Hb assessment was repeated using a finger stick . Severely anemic women ( Hb < 70 g/L ) were treated according to WHO recommendations . Folic acid alone had no effect on maternal anemia or iron status . Hb concentrations were 14 g/L , [ 95 % confidence limits ( CL ) , 8.3 - 19.2 ] , 10.0 g/L ( CL , 5.2 - 14.8 ) and 9.4 g/L ( CL , 4.7 - 14.1 ) higher in the groups receiving folic acid plus iron , folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients , respectively , relative to the control . Anemia in the third trimester was reduced by 54 % with folic acid plus iron , by 48 % with folic acid plus iron and zinc and by 36 % with folic acid plus iron , zinc and multiple micronutrients supplementation , relative to the control ( P < 0.05 ) . Thus , the combinations of folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients provided no additional benefit in improving maternal hematologic status during pregnancy compared with folic acid plus iron . The level of compliance and baseline Hb concentrations modified the effect of iron BACKGROUND Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements . The supply of both folic acid and docosahexaenoic acid ( DHA ) has been related to positive pregnancy and infant outcomes . OBJECTIVE We aim ed to assess whether fish-oil ( FO ) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid ( n-3 LC-PUFA ) status . DESIGN We conducted a multicenter ( Germany , Hungary , and Spain ) , r and omized , double-blind , 2 x 2 factorial , placebo-controlled trial . From gestation week 22 until delivery , 311 pregnant women received daily a preparation with FO [ 0.5 g DHA and 0.15 g eicosapentaenoic acid ( EPA ) ] , 400 microg methyltetrahydrofolic acid ( MTHF ) , FO with MTHF , or placebo . Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery , indicators of pregnancy outcome , and fetal development . RESULTS FO significantly ( P<0.001 ) increased maternal DHA and EPA ( % by wt ) , as shown by 3-factor repeated- measures ANOVA ( ie , MTHF , FO , and time ) with adjustment for maternal baseline DHA and EPA . In addition , FO significantly ( P<0.001 ) increased cord blood DHA ( % by wt ; 2-factor ANOVA ) . MTHF was significantly ( P=0.046 ) associated with increased maternal DHA ( % by wt ) . There was no FO x MTHF interaction for the time course of DHA or EPA ( P=0.927 and 0.893 ) . Pregnancy outcomes and fetal development did not differ significantly among the intervention groups . CONCLUSIONS FO supplementation from gest 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Efforts to determine the impact of prenatal multivitamin supplementation on birth outcome have been carried out in several developing countries . A review of factors that would impact the effectiveness of prenatal supplementation under normal field conditions is currently lacking and will be required for exp and ed supplementation programs . An efficacy trial of a multiple micronutrient supplement for pregnant women was conducted in rural western China , and additional information on side effects , rates of adherence , program inputs , and cost was also gathered . Objectives To examine reports of side effects and rates of adherence to prenatal multiple micronutrient supplementation in comparison with supplementation with folic acid and with iron – folic acid , and to describe inputs and costs associated with prenatal supplementation in China . Methods A cluster-r and omized , double-blind , controlled trial was conducted in two rural counties in northwest China . All pregnant women in villages were r and omly assigned to take daily supplements of folic acid , iron – folic acid , or a recommended daily allowance of 15 vitamins and minerals from enrollment until delivery . Information was collected from the women on side effects and adherence . Program inputs and costs of supplementation were tracked . Descriptive statistics were used for the analysis . The biological effectiveness of prenatal multiple micronutrient supplements is reported elsewhere . Results Less than 4 % of women withdrew from the study because of side effects . Adherence to supplementation was high : the supplements were consumed on more than 90 % of the days on which they were available for consumption . The mean number of supplements consumed was high at 165 capsules , and about 40 % consumed the recommended 180 supplements during pregnancy . Conclusions High adherence to a prenatal supplement schedule can be achieved when mothers have frequent contact with trained health workers and a reliable supply of supplements 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 In a controlled , prospect i ve 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 practice s in South-east Engl and .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 UNLABELLED Sulfadoxine-pyrimethamine ( SP ) inhibits folate metabolism by the malaria parasite . We investigated the association between folate levels and SP failure in pregnant women . Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed . Plasma folate levels were determined at enrollment and at day 7 . High baseline folate levels , high parasite densities , and age < 20 years were risk factors for SP failure . High-dose ( 5 mg daily ) folate supplementation or high folate levels at day 7 were independent risk factors . Therefore , pregnant women receiving SP should receive low-/moderate-dose folate supplementation . TRIAL REGISTRATION http://www . clinical trials.gov identifier : NCT00130065 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 The hypothesis was tested that the additional dietary uptake of n-3 fatty acids , in particular of DHA and 5-methyltetrahydrofolate ( 5-MTHF ) , during the second half of pregnancy would influence proliferation and apoptosis in the full-term human placenta . The diets of pregnant women from Spain ( n 55 ) were supplemented with modified fish oil and /or 5-MTHF or placebo , and assigned in a r and om , double-blind manner to one of the four groups . Immunohistochemistry and immunoblotting were used to detect placental proliferation and apoptosis with monoclonal antibodies for key proteins that reflected the extent of both processes : proliferation cell nuclear antigen ( PCNA ) , p53 , cytokeratin 18 neoepitope . The PCNA level in the fish oil/5-MTHF-treated group was higher by 66 % ( P < 0.05 ) than that of the placebo group , whereas the levels of p53 and cytokeratin 18 neoepitope were unaffected by treatment . PCNA expression was altered only in the trophoblast compartment ( placebo 11.1 ( se 0.5 ) % v. combination 21.5 ( se 1.2 ) % ; P < 0.05 ) , whereas the proportion of nuclei stained in endothelial and other stromal cells was similar in the placebo and combined treatment groups . No correlation was found between fish oil or 5-MTHF supplementation and the levels of the proteins . The present data suggest that supplementation with fish oil and /or 5-MTHF had no effect on the parameters reflecting placental proliferation and apoptosis . A defined combination of DHA and 5-MTHF may , however , affect placental proliferation Iron deficiency is one of the main causes of anemia during pregnancy , although other micronutrient deficiencies may play a role . We examined the effects of daily antenatal and postnatal supplementation with four combinations of micronutrients on  maternal hematologic indicators  in a double-masked r and omized controlled community trial . Communities , called sectors , were r and omly assigned to supplementation with folic acid ( 400 microg ) , folic acid plus iron ( 60 mg ) , folic acid plus iron and zinc ( 30 mg ) and folic acid plus iron , zinc and 11 other micronutrients , each at the approximate recommended daily allowance for pregnancy all given with vitamin A as retinol acetate ( 1000 microg retinol equivalent ) , or vitamin A alone as the control group .  Hemoglobin ( Hb ) and indicators of iron status were assessed at baseline and at 32 wk of gestation . At 6-wk postpartum , Hb assessment was repeated using a finger stick . Severely anemic women ( Hb < 70 g/L ) were treated according to WHO recommendations . Folic acid alone had no effect on maternal anemia or iron status . Hb concentrations were 14 g/L , [ 95 % confidence limits ( CL ) , 8.3 - 19.2 ] , 10.0 g/L ( CL , 5.2 - 14.8 ) and 9.4 g/L ( CL , 4.7 - 14.1 ) higher in the groups receiving folic acid plus iron , folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients , respectively , relative to the control . Anemia in the third trimester was reduced by 54 % with folic acid plus iron , by 48 % with folic acid plus iron and zinc and by 36 % with folic acid plus iron , zinc and multiple micronutrients supplementation , relative to the control ( P < 0.05 ) . Thus , the combinations of folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients provided no additional benefit in improving maternal hematologic status during pregnancy compared with folic acid plus iron . The level of compliance and baseline Hb concentrations modified the effect of iron BACKGROUND Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements . The supply of both folic acid and docosahexaenoic acid ( DHA ) has been related to positive pregnancy and infant outcomes . OBJECTIVE We aim ed to assess whether fish-oil ( FO ) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid ( n-3 LC-PUFA ) status . DESIGN We conducted a multicenter ( Germany , Hungary , and Spain ) , r and omized , double-blind , 2 x 2 factorial , placebo-controlled trial . From gestation week 22 until delivery , 311 pregnant women received daily a preparation with FO [ 0.5 g DHA and 0.15 g eicosapentaenoic acid ( EPA ) ] , 400 microg methyltetrahydrofolic acid ( MTHF ) , FO with MTHF , or placebo . Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery , indicators of pregnancy outcome , and fetal development . RESULTS FO significantly ( P<0.001 ) increased maternal DHA and EPA ( % by wt ) , as shown by 3-factor repeated- measures ANOVA ( ie , MTHF , FO , and time ) with adjustment for maternal baseline DHA and EPA . In addition , FO significantly ( P<0.001 ) increased cord blood DHA ( % by wt ; 2-factor ANOVA ) . MTHF was significantly ( P=0.046 ) associated with increased maternal DHA ( % by wt ) . There was no FO x MTHF interaction for the time course of DHA or EPA ( P=0.927 and 0.893 ) . Pregnancy outcomes and fetal development did not differ significantly among the intervention groups . CONCLUSIONS FO supplementation from gest 
    Output:
    