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Article ; Online: A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance.

Anisul, Mohd / Shilts, Jarrod / Schwartzentruber, Jeremy / Hayhurst, James / Buniello, Annalisa / Shaikho Elhaj Mohammed, Elmutaz / Zheng, Jie / Holmes, Michael / Ochoa, David / Carmona, Miguel / Maranville, Joseph / Gaunt, Tom R / Emilsson, Valur / Gudnason, Vilmundur / McDonagh, Ellen M / Wright, Gavin J / Ghoussaini, Maya / Dunham, Ian

eLife

2021 Volume 10

Abstract: Background: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19.: Methods: To identify host proteins that may contribute to the risk of severe ... ...

Abstract	Background: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19. Methods: To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets. Results: Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 × 10 Conclusions: Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19. Funding: MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
MeSH term(s)	2',5'-Oligoadenylate Synthetase/genetics ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19/virology ; Cell Adhesion Molecules ; Genome-Wide Association Study ; Humans ; Lectins, C-Type ; Proteome ; Receptors, Cell Surface ; SARS-CoV-2/physiology ; Scavenger Receptors, Class A/genetics ; Severity of Illness Index ; fas Receptor/genetics
Chemical Substances	Cell Adhesion Molecules ; DC-specific ICAM-3 grabbing nonintegrin ; FAS protein, human ; Lectins, C-Type ; Proteome ; Receptors, Cell Surface ; SCARA5 protein, human ; Scavenger Receptors, Class A ; fas Receptor ; OAS1 protein, human (EC 2.7.7.-) ; 2',5'-Oligoadenylate Synthetase (EC 2.7.7.84)
Language	English
Publishing date	2021-08-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.69719
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Article ; Online: Plasma triglycerides as a risk factor for chronic kidney disease in type 2 diabetes mellitus: Evidence from northeastern Thailand.

Zaman, Sojib Bin / Karim, Mohd Anisul / Hossain, Naznin / Al Kibria, Gulam Muhammed / Islam, Sheikh Mohammed Shariful

Diabetes research and clinical practice

2018 Volume 138, Page(s) 238–245

Abstract: Aims: To investigate the observational association between plasma triglyceride and CKD in patients with T2DM.: Methods: A hospital-based retrospective registry was used to obtain data of 3,748 T2DM patients from May 2016 to October 2016. ... ...

Abstract	Aims: To investigate the observational association between plasma triglyceride and CKD in patients with T2DM. Methods: A hospital-based retrospective registry was used to obtain data of 3,748 T2DM patients from May 2016 to October 2016. Anthropometric measurements and biochemical reports of T2DM patients with CKD were obtained by data extraction of medical records. CKD was defined according to the estimated glomerular filtration rate (eGFR< 60 mL/min/1.73 m Results: The mean age of the participants was 61.4 ± 11.0 years, and a majority of them was female (64%) with poor glycemic control (83%), increased plasma triglyceride (51%) and 27% of T2DM patients had CKD. There was a significant trend towards deteriorating renal function (lower eGFR) with categorically raised triglyceride levels. After controlling for age, sex and other confounders, 'borderline high' (adjusted odds ratio (OR): 1.24, 95% confidence interval (CI): 1.01-1.54), 'high' (adjusted OR: 1.52, 95% CI: 1.24-1.85) and 'very high' (adjusted OR: 3.40, 95% CI: 1.94-5.94) triglyceride level groups had higher likelihood to have CKD compared to normal triglyceride level. Conclusion: CKD was associated with a higher level of plasma triglyceride among patients with T2DM. These results support the rationale to screen and manage increased triglyceride in routine clinical practices among persons with diabetes to prevent CKD.
MeSH term(s)	Adult ; Aged ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Diabetic Nephropathies/blood ; Diabetic Nephropathies/diagnosis ; Diabetic Nephropathies/epidemiology ; Diabetic Nephropathies/etiology ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Prognosis ; Renal Insufficiency, Chronic/blood ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Retrospective Studies ; Risk Factors ; Thailand/epidemiology ; Triglycerides/blood
Chemical Substances	Triglycerides
Language	English
Publishing date	2018-04
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2018.02.011
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Article ; Online: Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.

Bomba, Lorenzo / Walter, Klaudia / Guo, Qi / Surendran, Praveen / Kundu, Kousik / Nongmaithem, Suraj / Karim, Mohd Anisul / Stewart, Isobel D / Langenberg, Claudia / Danesh, John / Di Angelantonio, Emanuele / Roberts, David J / Ouwehand, Willem H / Dunham, Ian / Butterworth, Adam S / Soranzo, Nicole

American journal of human genetics

2022 Volume 109, Issue 6, Page(s) 1038–1054

Abstract: Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective ...

Abstract	Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.
MeSH term(s)	Exome/genetics ; Gene Frequency/genetics ; Humans ; Prospective Studies ; Exome Sequencing/methods ; Whole Genome Sequencing
Language	English
Publishing date	2022-05-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2022.04.009
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Zs.A 107: Show issues

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Article ; Online: Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity.

Zheng, Jie / Zhang, Yuemiao / Zhao, Huiling / Liu, Yi / Baird, Denis / Karim, Mohd Anisul / Ghoussaini, Maya / Schwartzentruber, Jeremy / Dunham, Ian / Elsworth, Benjamin / Roberts, Katherine / Compton, Hannah / Miller-Molloy, Felix / Liu, Xingzi / Wang, Lin / Zhang, Hong / Smith, George Davey / Gaunt, Tom R

EBioMedicine

2022 Volume 81, Page(s) 104112

Abstract: Background: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ... ...

Abstract	Background: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries. Methods: In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritise drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions. Findings: MR and colocalization prioritized four protein targets, FCRL3, ICAM5, ENTPD5 and OAS1 that showed effect on COVID-19 severity in European ancestry. One protein target, SERPINA1 showed a stronger effect in African ancestry but much weaker effect in European ancestry (odds ratio [OR] in Africans=0.369, 95%CI=0.203 to 0.668, P = 9.96 × 10 Interpretation: Our study identified six proteins as showing putative causal effects on COVID-19 severity. OAS1 and SERPINA1 were targets of existing drugs in trials as potential COVID-19 treatments. ICAM1, ICAM5 and FCRL3 are related to the immune system. Across the six targets, OAS1 has no reliable instrument in African ancestry; SERPINA1, FCRL3, ICAM5 and ENTPD5 showed a different level of putative causal evidence in European and African ancestries, which highlights the importance of more powerful ancestry-specific GWAS and value of multi-ancestry MR in informing the effects of drug targets on COVID-19 across different populations. This study provides a first step towards clinical investigation of beneficial and adverse effects of COVID-19 drug targets. Funding: No.
MeSH term(s)	COVID-19/genetics ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Odds Ratio ; Phenotype ; Polymorphism, Single Nucleotide ; COVID-19 Drug Treatment
Language	English
Publishing date	2022-06-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2022.104112
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Article ; Online: An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci.

Mountjoy, Edward / Schmidt, Ellen M / Carmona, Miguel / Schwartzentruber, Jeremy / Peat, Gareth / Miranda, Alfredo / Fumis, Luca / Hayhurst, James / Buniello, Annalisa / Karim, Mohd Anisul / Wright, Daniel / Hercules, Andrew / Papa, Eliseo / Fauman, Eric B / Barrett, Jeffrey C / Todd, John A / Ochoa, David / Dunham, Ian / Ghoussaini, Maya

Nature genetics

2021 Volume 53, Issue 11, Page(s) 1527–1533

Abstract: Genome-wide association studies (GWASs) have identified many variants associated with complex traits, but identifying the causal gene(s) is a major challenge. In the present study, we present an open resource that provides systematic fine mapping and ... ...

Abstract	Genome-wide association studies (GWASs) have identified many variants associated with complex traits, but identifying the causal gene(s) is a major challenge. In the present study, we present an open resource that provides systematic fine mapping and gene prioritization across 133,441 published human GWAS loci. We integrate genetics (GWAS Catalog and UK Biobank) with transcriptomic, proteomic and epigenomic data, including systematic disease-disease and disease-molecular trait colocalization results across 92 cell types and tissues. We identify 729 loci fine mapped to a single-coding causal variant and colocalized with a single gene. We trained a machine-learning model using the fine-mapped genetics and functional genomics data and 445 gold-standard curated GWAS loci to distinguish causal genes from neighboring genes, outperforming a naive distance-based model. Our prioritized genes were enriched for known approved drug targets (odds ratio = 8.1, 95% confidence interval = 5.7, 11.5). These results are publicly available through a web portal ( http://genetics.opentargets.org ), enabling users to easily prioritize genes at disease-associated loci and assess their potential as drug targets.
MeSH term(s)	Chromosome Mapping/methods ; Epigenomics ; Genome-Wide Association Study/methods ; Genome-Wide Association Study/statistics & numerical data ; Genomics/methods ; Humans ; Machine Learning ; Models, Genetic ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
Language	English
Publishing date	2021-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-021-00945-5
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Article ; Online: A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

Mohd Anisul / Jarrod Shilts / Jeremy Schwartzentruber / James Hayhurst / Annalisa Buniello / Elmutaz Shaikho Elhaj Mohammed / Jie Zheng / Michael Holmes / David Ochoa / Miguel Carmona / Joseph Maranville / Tom R Gaunt / Valur Emilsson / Vilmundur Gudnason / Ellen M McDonagh / Gavin J Wright / Maya Ghoussaini / Ian Dunham

eLife, Vol

2021 Volume 10

Abstract: Background: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19. Methods: To identify host proteins that may contribute to the risk of severe COVID-19, ...

Abstract	Background: The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19. Methods: To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets. Results: Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 × 10-4), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. Conclusions: Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19. Funding: MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Keywords	COVID-19 ; proteins ; mendelian randomization ; genetic colocalization ; apoptosis ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A community-based cluster randomised controlled trial to evaluate the effectiveness of different bundles of nutrition-specific interventions in improving mean length-for-age z score among children at 24 months of age in rural Bangladesh

Sk Masum Billah / Tarana E. Ferdous / Mohd Anisul Karim / Michael J. Dibley / Shahreen Raihana / Md Moinuddin / Nuzhat Choudhury / Tahmeed Ahmed / D. M. Emdadul Hoque / Purnima Menon / Shams El Arifeen

BMC Public Health, Vol 17, Iss 1, Pp 1-

study protocol

2017 Volume 12

Abstract: Abstract Background Prevalence of stunting among under-five children in Bangladesh is 36%, varying with geographic and socio-economic characteristics. Previously, research groups statistically modelled the effect of 10 individual nutrition-specific ... ...

Abstract	Abstract Background Prevalence of stunting among under-five children in Bangladesh is 36%, varying with geographic and socio-economic characteristics. Previously, research groups statistically modelled the effect of 10 individual nutrition-specific interventions targeting the critical first 1000 days of life from conception, on lives saved and costs incurred in countries with the highest burden of stunted children. However, primary research on the combined effects of these interventions is limited. Our study directly addresses this gap by examining the effect of combinations of 5 preventive interventions on length-for-age z-scores (LAZ) among 2-years old children. Methods This community-based cluster randomised trial (c-RCT) compares 4 intervention combinations against one comparison arm. Intervention combinations are: 1) Behaviour change communication (BCC) on maternal nutrition during pregnancy, exclusive breastfeeding, and complementary feeding, along with prenatal nutritional supplement (PNS) and complementary food supplement (CFS); 2) BCC with PNS; 3) BCC with CFS; and 4) BCC alone. The comparison arm receives only routine health and nutrition services. From a rural district, 125 clusters were selected and randomly assigned to any one of the five study arms by block randomisation. A bespoke automated tab-based system was developed linking data collection, intervention delivery and project supervision. Total sample size is 1500 pregnant women, with minimum 1050 resultant children expected to be retained, powered to detect a difference of at least 0.4 in the mean LAZ score of children at 24 months, the main outcome variable, between the comparison arm and each intervention arm. Length and other anthropometric measurements, nutritional intake and other relevant data on mother and children are being collected during enrolment, twice during pregnancy, postpartum monthly till 6 months, and every third month thereafter till 24 months. Discussion This c-RCT explores the effectiveness of bundles of preventive ...
Keywords	Randomised controlled trial ; Bundling ; Nutrition interventions ; Stunting ; Length-for-age ; First 1000 days of life ; Public aspects of medicine ; RA1-1270
Subject code	360
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

Karim, Mohd Anisul / Shilts, Jarrod / Schwartzentruber, Jeremy / Hayhurst, James / Buniello, Annalisa / Mohammed, Elmutaz Shaikho Elhaj / Zheng, Jie / Holmes, Michael V. / Ochoa, David / Carmona, Miguel / Maranville, Joseph / Gaunt, Tom R. / Emilsson, Valur / Gudnason, Vilmundur / McDonagh, Ellen M. / Wright, Gavin J. / Ghoussaini, Maya / Dunham, Ian

medRxiv

Abstract: The virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1), interleukin-6 ... ...

Abstract	The virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1), interleukin-6 signalling (IL-6R), and the coagulation cascade (linked via ABO) that were associated with risk of COVID-19. In the present study, we performed proteome-wide genetic colocalisation tests leveraging publicly available protein and COVID-19 datasets, to identify additional proteins that may contribute to COVID-19 risk. Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble FAS (colocalisation probability > 0.9, p = 1 x 10<sup>-4</sup>), implicating FAS-mediated apoptosis as a potential target for COVID-19 risk. We also undertook polygenic (pan) and cis-Mendelian randomisation analyses that showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal was associated with plasma concentrations of several proteins, with the strongest association observed with CD209 in several proteomic datasets. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.
Keywords	covid19
Language	English
Publishing date	2021-03-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.15.21253625
Database	COVID19

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Article ; Online: Bangladesh: a success case in combating childhood diarrhoea.

Billah, Sk Masum / Raihana, Shahreen / Ali, Nazia Binte / Iqbal, Afrin / Rahman, Mohammad Masudur / Khan, Abdullah Nurus Salam / Karim, Farhana / Karim, Mohd Anisul / Hassan, Aniqa / Jackson, Bianca / Walker, Neff / Hossain, M Altaf / Sarker, Sukumar / Black, Robert E / El Arifeen, Shams

Journal of global health

2019 Volume 9, Issue 2, Page(s) 20803

Abstract: Background: Bangladesh had a large reduction in childhood deaths due to diarrhoeal disease in recent decades. This paper explores the preventive, promotive, curative and contextual drivers that helped Bangladesh achieve this exemplary success.: ... ...

Abstract	Background: Bangladesh had a large reduction in childhood deaths due to diarrhoeal disease in recent decades. This paper explores the preventive, promotive, curative and contextual drivers that helped Bangladesh achieve this exemplary success. Methods: Primary and secondary data collection approaches were used to document trends in reduction of Diarrhoea Specific Mortality Rate (DSMR) between 1980 and 2015, understand what policies and programmes played key roles, and estimate the contribution of specific interventions that were implemented during the period. Data acquisition involved relevant document reviews and in-depth interviews with key stake-holders. A systematic search of literature was undertaken to explore socio-economic, aetiological, behavioural, and nutritional drivers of diarrhoeal disease reduction in Bangladesh. Finally, we used LiST (Lives Saved Tool) to model the contributions of the relevant interventions during three time periods (1980-2015, 1980-2000 and 2000-2015), and to project the number of lives saved in 2030 (compared to 2015) if these interventions were implemented at near universal coverage (90%). Results: The factors which likely had the most impact on DSMR were the coordinated efforts of the Government of Bangladesh (GoB) with non-government organizations (NGOs) and the private sector that enabled swift implementation, at scale, of interventions like oral rehydration solution (ORS) and zinc, promotion of breastfeeding, handwashing and sanitary latrines (WASH), as well as improvements in female education and nutrition. Compared to 1980, we found ORS and reduction in stunting prevalence had the greatest impact on DSMR, saving roughly 70 000 lives combined in 2015. Until 2000, ORS had a higher contribution to DSMR reduction than reduction in stunting prevalence. This proportionate contribution was reversed during 2000-2015. At near universal coverage (90%) of combined direct diarrhoeal disease, nutrition and WASH interventions, we project that an additional 5356 deaths due to diarrhoea could be averted in 2030. Conclusion: Bangladesh's achievement in reduction of DSMR highlights the important role of an enabling policy environment that fostered coordinated efforts of the public and private sectors and NGOs for maximal impact. To maintain this momentum, evidence-based interventions should be scaled up at universal coverage.
MeSH term(s)	Achievement ; Bangladesh/epidemiology ; Child Mortality/trends ; Child, Preschool ; Diarrhea/mortality ; Diarrhea/prevention & control ; Humans ; Infant ; Infant Mortality/trends ; Infant, Newborn ; Program Evaluation
Language	English
Publishing date	2019-07-08
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	2741629-X
ISSN	2047-2986 ; 2047-2986
ISSN (online)	2047-2986
ISSN	2047-2986
DOI	10.7189/jogh.09.020803
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Article ; Online: A community-based cluster randomised controlled trial to evaluate the effectiveness of different bundles of nutrition-specific interventions in improving mean length-for-age z score among children at 24 months of age in rural Bangladesh: study protocol.

Billah, Sk Masum / Ferdous, Tarana E / Karim, Mohd Anisul / Dibley, Michael J / Raihana, Shahreen / Moinuddin, Md / Choudhury, Nuzhat / Ahmed, Tahmeed / Hoque, D M Emdadul / Menon, Purnima / Arifeen, Shams El

BMC public health

2017 Volume 17, Issue 1, Page(s) 375

Abstract: Background: Prevalence of stunting among under-five children in Bangladesh is 36%, varying with geographic and socio-economic characteristics. Previously, research groups statistically modelled the effect of 10 individual nutrition-specific ... ...

Abstract	Background: Prevalence of stunting among under-five children in Bangladesh is 36%, varying with geographic and socio-economic characteristics. Previously, research groups statistically modelled the effect of 10 individual nutrition-specific interventions targeting the critical first 1000 days of life from conception, on lives saved and costs incurred in countries with the highest burden of stunted children. However, primary research on the combined effects of these interventions is limited. Our study directly addresses this gap by examining the effect of combinations of 5 preventive interventions on length-for-age z-scores (LAZ) among 2-years old children. Methods: This community-based cluster randomised trial (c-RCT) compares 4 intervention combinations against one comparison arm. Intervention combinations are: 1) Behaviour change communication (BCC) on maternal nutrition during pregnancy, exclusive breastfeeding, and complementary feeding, along with prenatal nutritional supplement (PNS) and complementary food supplement (CFS); 2) BCC with PNS; 3) BCC with CFS; and 4) BCC alone. The comparison arm receives only routine health and nutrition services. From a rural district, 125 clusters were selected and randomly assigned to any one of the five study arms by block randomisation. A bespoke automated tab-based system was developed linking data collection, intervention delivery and project supervision. Total sample size is 1500 pregnant women, with minimum 1050 resultant children expected to be retained, powered to detect a difference of at least 0.4 in the mean LAZ score of children at 24 months, the main outcome variable, between the comparison arm and each intervention arm. Length and other anthropometric measurements, nutritional intake and other relevant data on mother and children are being collected during enrolment, twice during pregnancy, postpartum monthly till 6 months, and every third month thereafter till 24 months. Discussion: This c-RCT explores the effectiveness of bundles of preventive nutrition intervention approaches addressing the critical window of opportunity to mitigate childhood stunting. The results will provide robust evidence as to which bundle(s) can have significant effect on linear growth of children. Our study also will have policy-level implications for prioritising intervention(s) tackling stunting. Trial registration: The study was retrospectively registered on May 2, 2016 and is available online at ClinicalTrials.gov (ID: NCT02768181 ).
MeSH term(s)	Anthropometry ; Bangladesh ; Breast Feeding ; Child Development ; Child, Preschool ; Dietary Supplements ; Female ; Growth Disorders/prevention & control ; Health Behavior ; Humans ; Infant ; Infant Nutritional Physiological Phenomena ; Maternal Nutritional Physiological Phenomena ; Mothers ; Nutritional Status ; Patient Care Bundles ; Pregnancy ; Research Design ; Rural Population
Language	English
Publishing date	2017-05-02
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ISSN	1471-2458
ISSN (online)	1471-2458
DOI	10.1186/s12889-017-4281-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Inter-library loan at ZB MED

Full text online

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Inter-library loan at ZB MED

Full text online

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Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED