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Report for Clinical Trial NCT01795131

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Role of Vitamin B12 Supplementation During Pregnancy and Postpartum to Reduce Nutritional Anemia and Improve Immunity in Bangladeshi Women and Their Infants

Nutritional anemia is a major public health problem among children and women in developing countries. Despite ongoing national program of supplementing pregnant women with iron-folate, prevalence of anemia is 39% among pregnant women and 78% among infants in Bangladesh. Vitamin B12 deficiency is a more prevalent cause of megaloblastic anemia than folate in many developing countries. This data raises the interest to address the role of vitamin B12 deficiency in nutritional anemia. Low dietary intake of animal products, a predominant source of vitamin B12 may cause anemia. Besides maintaining normal erythropoiesis, B12 is essential for immune function. However, no studies have evaluated the effect of maternal B12 supplementation on reduction of anemia and improving immunity of their infants. The investigators hypothesize that vitamin B12 supplementation plus iron-folate during pregnancy and 3-mo postpartum would: (a) Decrease anemia among mothers and infants; (b) Improve vaccine specific cellular and humoral immune responses among mothers; (c) Improve vaccine specific immunity in infants by passive transfer; (d) Improve DNA methylation and one-carbon metabolism in mother-child pairs; (e) Reduce antenatal/postnatal depression. Results from this study will guide and provide support to the policy makers to identify effective strategies to reduce nutritional anemia in population at risk. The investigators aim to conduct a double-masked placebo controlled trial to investigate the added effect of vitamin B12 on the iron-folate supplementation among pregnant women. Anemic (Hb level <11.0 g/dl) mothers at 11-14 weeks of gestation will be randomized into two groups: supplement group will receive 250 ug vitamin B12 plus 400 ug folate and 60 mg iron; placebo group will receive folate and iron only. This daily supplementation will continue up to 3-mo postpartum. At 26-28 wk of gestation mothers will be given inactivated influenza vaccine. Data on anthropometric indices of mothers and children, birth size, infant growth and morbidity (mothers and children) throughout the study period will be recorded. 24-h dietary recall data will be collected from the mothers bimonthly throughout the study. Biochemical indicators of anemia including Hb, vitamin B12, ferritin, folate and α-glycoprotein (AGP) will be assessed in plasma of mothers (pre- and post-supplementation) and infants (cord blood and 3-months). Additional measurements include serum transferrin receptor (sTfR) in plasma and methyl malonic acid (MMA) and total homocysteine (tHcy) in the urine of mothers. Plasma vaccine specific antibody responses will be measured in mothers (pre- and post supplementation) and in infants (cord blood and 3-months). In breast milk, B12, folate and s-IgA will be determined. Genetic polymorphism (one-carbon metabolism) and DNA methylation will be studied in mothers and in cord blood.

NCT01795131 Nutritional Anemia in Mothers. Nutritional Anemia in Infants.
MeSH:Anemia
HPO:Anemia

2 Interventions

Name: Vitamin B12

Type: Dietary Supplement
Group Labels: 1

Vitamin B12

Name: Placebo

Type: Dietary Supplement
Group Labels: 1

Placebo


Primary Outcomes

Description: The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, sTfR, B12 levels in plasma. They will also measure urinary MMA and tHcy and B12 levels in breast milk.

Measure: a) Percent reduction in nutritional anemia among mothers (based on measurement of Hb, ferritin, sTfR, folate, B12 levels in plasma; urinary MMA and tHcy; B12 levels in breast milk.)

Time: 24 months

Description: Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.

Measure: Increase in influenza vaccine specific cellular and humoral responses among mothers (blastogenesis and T cell phenotyping,serum IgA, and IgG).

Time: 24 monnths

Description: Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.

Measure: Increase in influenza vaccine specific immunity in infants by passive transfer (vaccine specific IgG in cord blood and breast milk and IgA in children at 3 mo).

Time: 24 months

Description: The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, B12 levels in plasma.

Measure: Percent reduction in nutritional anemia in infants (based on measurement of Hb, ferritin, B12 levels in plasma;

Time: 24 months

Secondary Outcomes

Description: Genomic DNA methylation will be measured by the methyl acceptance assay . Total homocysteine (tHcy) will be measured in urine samples by using HPLC with fluorimetric detection. Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing.

Measure: Effect of B12 status on DNA methylation and one-carbon metabolism in mother-child pairs.

Time: 24 months

Description: Participants will be interviewed on their mental status using the Centre for Epidemiological Studies-Depression questionnaire. The questionnaire contains 20 items comprising six major aspects of depression: depressed mood, hopelessness, worthlessness, fatigue, appetite and sleep disturbances. It has been previously used in rural and urban Bangladeshi women (J Hamadani) and found to correlate sensibly to children's growth and development. The interview will be conducted twice at the homes of the women first at baseline and at 3 mo postpartum.

Measure: Reduce depression scores

Time: 24 months

Purpose: Health Services Research

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 C677T

Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing.. Reduce depression scores. --- C677T ---

Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing. --- C677T ---



HPO Nodes


HPO:
HP:0001903: Anemia
Genes 730
SRD5A3 NDUFS7 CTC1 KLF1 TBXAS1 SRP54 IL2RG TET2 RPS27 AMMECR1 SLC25A38 MLX CD40LG ERCC6L2 RPS24 YARS2 CFI DCLRE1C SCARB2 ALX4 UBE2T MPL TSR2 EXT2 MUC1 XRCC4 VPS33A FAM111A EFL1 WT1 FASLG TSR2 PNPO RPS29 SDHC BCL10 LAMC2 OCRL CHD7 TINF2 FOXP3 NT5C3A ENG PRKCD CR2 PLEKHM1 CASK IRAK1 DAXX MALT1 PKLR GBA TINF2 PSMB8 ZBTB20 SLC4A1 WFS1 NHEJ1 TACO1 RPL35A TCIRG1 FLI1 BMPR1A TNFSF12 CFI BMPR1A SMAD4 LAT ACVR1 COX10 ALAS2 MTRR FOXP1 LYRM7 DHFR TERT DNAJC21 RPL15 HBA1 CTSK KLF1 PGK1 HBB HBB CLCNKB RPS10 MTHFD1 FASTKD2 G6PC3 AASS BRCA1 ANK1 UROS EPB42 TEK FASLG SBDS NHP2 MYSM1 CD81 TNFSF12 RHAG CFH SMAD4 HBB LRBA NDUFS3 STEAP3 CDCA7 DNAJC21 CP DCLRE1C HMGCL RMRP XRCC2 RAG1 PGK1 F8 HELLPAR NFKB2 RECQL4 NPHP4 EPO RHAG COX6B1 REN COL7A1 SPTB RPL35 CD46 PALB2 RAG2 NDUFB8 SRD5A3 FTCD FCGR2A COX8A HPRT1 PTF1A WAS TBCE SPTA1 KDM6A FANCE ICOS SLC11A2 CLPX NFKB1 FCGR2B CA2 KIF23 HLA-DRB1 FAS ALAD RPL26 RAD51 EWSR1 MMAA SLC4A1 CAT NDUFS2 STAT3 SLC2A1 ADA2 EPB41 C1R APOA1 GBA ATRX FANCD2 TET2 UMPS SLCO2A1 ATP11C ACVRL1 KRT14 RTEL1 RPL5 ITGB3 GLA TMEM67 FANCC HBA2 DNMT3B HBA1 LAMA3 TNFSF11 BIRC3 SDHA RPS14 IFNG HAVCR2 IRF2BP2 RPS19 RPL35A PEPD TCIRG1 SPTA1 ACVRL1 GLA PIGA FANCL YARS2 STK11 NDUFA12 GPI SNX10 ECHS1 THRA RPL27 APC NDUFV2 ACD BCOR MTRR GBA ALAS2 ERCC4 PIEZO1 RPL26 HBG1 MVK AK1 STAT1 MTFMT CFB SBDS WAS NFKB1 AK2 IFT140 PFKM MMACHC RPS24 RNF113A HMGCL UMPS SLC4A1 HBB GATA1 BRCA1 TRNS1 PARN ZBTB24 STIM1 RFWD3 KIF15 PCCA HBA1 NDUFS2 ITGB4 PSMB4 DNASE1 HBA2 ABCD3 ALDOA RPS28 TET2 COL7A1 ACTN4 SMPD1 RPS17 ABCB7 ABCA1 ZBTB16 NUMA1 TINF2 DKC1 BMPR1A LIG4 RPS7 AGGF1 NDUFAF6 RAG1 UROS KCNN4 IREB2 NPHP1 RPL15 SLC2A1 FMO3 RPS27 RPS26 KIT ALPL HYOU1 STAT5B HPGD GBA C1QA TGFB1 SLX4 RAG2 TERC BMPR1A MMUT KCNN4 HMOX1 FANCB LAMA3 RPS28 SLC19A3 FANCA MPL STIM1 ELANE FANCC CD46 PET100 PGM3 SLC4A1 MAD2L2 ERCC2 EPHB4 KRAS FOXP3 RPS7 MMUT TGFB1 CD19 HBG2 KIT SARS2 SBDS WRAP53 GCLC COX14 EFL1 COX4I2 ORAI1 STING1 NABP1 CRIPT PUS1 CA2 FARS2 ERCC3 SLC19A2 WIPF1 SLC25A13 TERC DKC1 NSUN2 TRNN PHKG2 ETV6 NBN NDUFV1 STAT3 SP110 UBR1 PUS1 PRF1 RARA PHGDH IL2RB FERMT3 ATP7B RPL27 PET100 LCAT LAMB3 C3 COL7A1 HLA-B NLRC4 ENG CD59 COX15 NDUFA10 TERT TF TNFAIP3 LPIN2 MECOM PIGT DNAJC19 NDUFS1 PRF1 DNAJC19 GALT ITK PTEN PRKCD LIPA ABCD4 IDH1 STK11 RPL11 ATRX LPIN2 GATA1 NPM1 TPP2 SAMD9L ALAS2 KIF1B CD3G NDUFAF3 EPB41 ABCG8 SLC12A3 HBB POLG PRDX1 WFS1 NRAS CISD2 GLRX5 PRKAR1A LAMC2 COA8 OSTM1 RPS29 ATRX SCO2 NLRP3 SLC46A1 DGKE FIP1L1 MYSM1 UBE2T CPOX SLC29A3 LAMB3 TRNT1 TACO1 COL7A1 HBD SPTB NDUFA9 MTR PML GSS SMAD4 TRNT1 TBL1XR1 HBA1 SRP54 SHPK RPL18 SMARCAL1 SPTA1 ISCU DNM1L ELANE MARS1 IDH2 RPS26 GNA14 CAD IL7R COX20 GREM1 FANCE MMP1 HBA1 NDUFAF2 FANCL RFX5 NPHP1 ATP7B ATRX HBB HSPA9 CLCN7 JAK2 TPI1 MPIG6B SLC40A1 PSAP FOXRED1 LIG4 PHGDH SURF1 TERC FANCG SF3B1 KMT2D NOD2 BRIP1 SLC19A2 ADAMTS13 HBB RPL5 GATA1 NBN FANCF PDGFRA PSMB9 ALG8 FECH CP GYPC TALDO1 ABCB7 FAS PTH1R CLCN7 PCCB FAM111A HAMP CDAN1 PGM3 STIM1 DBH LMBRD1 ADA HBG2 GTF2E2 SMAD4 RPS17 STAT1 PARN RPS14 RFXANK RHAG TNFRSF13C TNFRSF13B STX11 CALR UROD ACAD8 NLRP3 PNP USB1 SEC23B RPL31 CIITA HBG1 RFXAP ADA LARS1 RAG2 RMRP COL4A1 FDX2 COQ2 PFKM COG1 CLCN7 BTK FANCA AMN NDUFA13 TF SEC61A1 NDUFS4 F2 SLC4A1 STEAP3 CASP10 ATRX GTF2H5 FANCM TARS1 KCNE1 RTEL1 SLC46A1 TNFSF11 ABCA1 CD55 PIEZO1 RBM8A ITGA2B CTLA4 PNPO SLC7A7 KCNQ1 RPS15A HELLS PLEC NDUFAF5 RPS10 SDHB ELMO2 HPRT1 HBB ANK1 MPLKIP ITGB4 RAG1 SAMD9L DDX41 IGH RAG1 SPTA1 IRX5 FANCD2 SDHA GDF2 COA8 GBA HBB TFRC RASGRP1 CASP10 TCIRG1 ADA2 NHLRC2 CASR COL7A1 PDHA1 BRCA2 PNP NPHP4 TNFRSF11A STAT4 RMRP PSMB8 RAD51C PCNT PLEC HBA2 HLA-B SH2D1A EPB42 SMARCD2 LARS2 ZAP70 RPL11 C15ORF41 SPTA1 IL2RA TCN2 PTPN22 SMARCAL1 TYMP MYD88 TFR2 GPX1 TREX1 SAMD9 BTNL2 PACS2 NDUFA4 SLX4 OPA1 GCLC NPM1 GATA1 COG6 IKZF1 PHKA2 ADAR SLC7A7 DKC1 NLRP1 MS4A1 VPS45 CFHR1 SCO1 RPS19 NDUFA2 PRKCD TMPRSS6 PLEKHM1 TP53 AIRE BPGM GATA1 FANCG RPS15A FANCI LYST TET2 TNFRSF4 CFHR3 MMP1 HBB SLC4A1 COL17A1 HBA2 LYST SNX10 HBB RRM2B CTLA4 PKLR IL12B PHF21A FERMT1 FANCB NDUFS8 SFXN4 HBB-LCR TERT GATA1 PRKACG XIAP SPP1 CUBN SPTB GSS CTC1 CCND1 TTC7A TTC7A NOP10 FARSB LIPT1 ABCB6 UNC13D IFNGR1 TRNW MMAB GATA1 PLA2G4A FAS HBB ANK1 CFH CLCN7 VPS33A SURF1 CBLIF TALDO1 AGXT HBA2 MMADHC HK1 GP1BA MAD2L2 ENG FECH G6PD TBXAS1 THBD TERT ERBB3
Protein Mutations 4
C282Y C677T H63D V617F