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Effectiveness of vitamin A supplementation for preventing morbidity and mortality in children: What's the evidence?

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Health Evidence™ hosted a 60 minute webinar examining the effectiveness of vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Click here for access to the audio recording for this webinar: https://youtu.be/fuWd7TJQYEI

Dr. Aamer Imdad, MBBS, MPH, Assistant Professor of Pediatrics, SUNY Upstate Medical University led the session and presented findings from their recent Cochrane review:

Imdad A, Mayo-Wilson E, Herzer K, & Bhutta Z. (2017). Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database of Systematic Reviews, 2017(3), CD008524.

Vitamin A deficiency is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. This review examines the effectiveness of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. Forty-seven randomized control trials involving approximately 1,223,856 children were included in this review. VAS was associated with a clinically meaningful reduction in morbidity and mortality in children.

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Effectiveness of vitamin A supplementation for preventing morbidity and mortality in children: What's the evidence?

  1. 1. Welcome! Effectiveness of vitamin A supplementation for preventing morbidity and mortality in children: What's the evidence? You will be placed on hold until the webinar begins. The webinar will begin shortly, please remain on the line.
  2. 2. Poll Questions: Consent • Participation in the webinar poll questions is voluntary • Names are not recorded and persons will not be identified in any way • Participation in the anonymous polling questions is accepted as an indication of your consent to participate Benefits: • Results inform improvement of the current and future webinars • Enable engagement; stimulate discussion. This session is intended for professional development. Some data may be used for program evaluation and research purposes (e.g., exploring opinion change) • Results may also be used to inform the production of systematic reviews and overviews Risks: None beyond day-to-day living
  3. 3. After Today • The PowerPoint presentation and audio recording will be made available • These resources are available at: – PowerPoint: http://www.slideshare.net/HealthEvidence – Audio Recording: https://www.youtube.com/user/healthevidence /videos 3
  4. 4. What’s the Evidence? Imdad A, Mayo-Wilson E, Herzer K, & Bhutta Z. (2017). Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database of Systematic Reviews, 2017(3), CD008524. https://healthevidence.org/view- article.aspx?a=vitamin-supplementation- preventing-morbidity-mortality-children- months-years-age-30222
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  6. 6. Housekeeping (cont’d) • Audio – Listen through your speakers – Go to ‘Communicate > Audio Broadcast’ • WebEx 24/7 help line – 1-866-229-3239
  7. 7. Poll Question #1 How many people are watching today’s session with you? A. Just me B. 2-3 C. 4-5 D. 6-10 E. >10
  8. 8. The Health Evidence™ Team Maureen Dobbins Scientific Director Heather Husson Manager Susannah Watson Project Coordinator Students: Emily Belita (PhD candidate) Jennifer Yost Assistant Professor Olivia Marquez Research Coordinator Emily Sully Research Assistant Liz Kamler Research Assistant Zhi (Vivian) Chen Research Assistant Research Assistants: Claire Howarth Rawan Farran Kristin Read Research Coordinator
  9. 9. What is www.healthevidence.org? Evidence Decision Making inform
  10. 10. Why use www.healthevidence.org? 1. Saves you time 2. Relevant & current evidence 3. Transparent process 4. Supports for EIDM available 5. Easy to use
  11. 11. A Model for Evidence- Informed Decision Making National Collaborating Centre for Methods and Tools. (revised 2012). A Model for Evidence-Informed Decision-Making in Public Health (Fact Sheet). [http://www.nccmt.ca/pubs/FactSheet_EIDM_EN_WEB.pdf]
  12. 12. Stages in the process of Evidence-Informed Public Health National Collaborating Centre for Methods and Tools. Evidence-Informed Public Health. [http://www.nccmt.ca/eiph/index-eng.html]
  13. 13. Poll Question #2 Have you heard of PICO(S) before? A.Yes B.No
  14. 14. Searchable Questions Think “PICOS” 1.Population (situation) 2.Intervention (exposure) 3.Comparison (other group) 4.Outcomes 5.Setting
  15. 15. How often do you use systematic reviews to inform a program/services? A.Always B.Often C.Sometimes D.Never E.I don’t know what a systematic review is Poll Question #3
  16. 16. Aamer Imdad PhD, MBBS, FRCPCH, FAAP, Co-Director, Director of Research Centre for Global Child Health, The Hospital for Sick Children, Senior Scientist, Research Institute, Professor Department of Nutritional Sciences, Professor, University of Toronto, Division of Epidemiology Dalla Lana School of Public Health MBBS, MPH, Assistant Professor of Pediatrics, SUNY Upstate Medical University Zulfiqar Bhutta
  17. 17. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age • Imdad A, Mayo-Wilson E, Herzer K, Bhutta ZA. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev. 2017 Mar 11;3:CD008524. • Imdad A, Herzer K, Mayo-Wilson E, Yakoob MY, Bhutta ZA. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD008524. • Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ. 2011 Aug 25;343:d5094. • Imdad A, Ahmed Z, Bhutta ZA. Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age. Cochrane Database Syst Rev. 2016 Sep 28;9:CD007480. • Haider BA, Sharma R, Bhutta ZA. Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in low and middle income countries. Cochrane Database Syst Rev. 2017 Feb 24;2:CD006980.
  18. 18. Background • What is vitamin A? – Essential micronutrient, subclass of retinoic acids, lipid- soluble compounds • What is the normal function of vitamin A? – Required for visual system, maintenance of cell function for growth, epithelial integrity, red blood cell production, immunity, and reproduction • What are the consequences of Vitamin A Deficiency (VAD)? – Xerophthalmia (dry eyes), Bitot spots, blindness, susceptibility to infection including diarrhea, pneumonia, measles, stunting, and anemia, and may cause death
  19. 19.  WHO estimates: 2009  19.1 million pregnant women  190 million (33%) children < 5 years  Most common cause of nutritional blindness in children  122 countries have a moderate to severe VAD public health problem  Recent estimates showed that VAD is decreasing but still prevalent in South East Asia and Sub-Saharan Africa How common is the VAD? Stevens et. Al Lancet Global Health 2015;3 (9):e528-36.
  20. 20. Background • What are the common sources of vitamin A?  Naturally: plants: inactive retinoids (provitamin: green leafy vegetables, yellow vegetables, and yellow/orange non-citrus fruits  Active form: animal based: retinol, retinal and retinoic acid: glandular meats, liver, fish liver oils, egg yolk, whole milk, dairy products and human milk • Why do we need to supplement vitamin A?  Bioavailability: carotenoid-to-retinol conversion ratio varies with type of food, ranging from 6:1 to 26:1  Increased losses due to increased burden of infectious disease, low consumption and increased losses due to diarrheal disease  Food insecurity
  21. 21. Objective To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years.
  22. 22. Methods
  23. 23. Methods • Study design: Systematic review and meta-analysis • Type of studies: Individual and cluster randomized controlled trials • Participants: Children 6 months to 5 years • Intervention: Preventive, synthetic vitamin A supplementation • Comparison: Placebo or no intervention
  24. 24. Methods • Outcomes:  Primary: – All-cause mortality  Secondary outcomes: – Cause-specific mortality: Diarrhea, pneumonia, measles – Cause-specific morbidity: Diarrhea, pneumonia, measles, night blindness – Side effects – Vitamin A deficiency status (based on serum retinol level)
  25. 25. Literature Searches • Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) (searched 1 March 2016). • MEDLINE Ovid (1946 to February Week 3 2016). • Medline In-Process & Other Non-Indexed Citations Ovid (29 February 2016). • Embase Ovid (1980 to 2016 Week 9). • Science Citation Index Web of Science (SCI; 1970 to 27 February 2016). • Conference Proceedings Citation Index - Science Web of Science (CPCI-S; 1990 to 27 February 2016). • Cochrane Database of Systematic Reviews (CDSR; 2016, Issue 2) in the Cochrane Library. • Database of Abstracts of Reviews of Effects (DARE; 2015 Issue 2) in the Cochrane Library. • LILACS (Latin American and Caribbean Health Science Information database (searched 1 March 2016). • African Index Medicus (searched 1 March 2016). • ClinicalTrials.gov (clinicaltrials.gov; searched 1 March 2016). • World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; searched 1 March 2016).
  26. 26. Data Synthesis • Data extraction: Double data abstraction • Risk of bias: Cochrane handbook of systematic reviews • Meta-analysis: Generic inverse variance: fixed effect models • Dichotomous variables: Risk ratios (95 % confidence interval) • Continuous variables: Standardized Mean difference with 95 % CI • Overall quality: GRADE criteria
  27. 27. Results
  28. 28. PRISMA Flow Diagram
  29. 29. Characteristics of Included Studies • Most of the studies were conducted in low and middle income countries • Sample size ranged from 35 to 1 million and overall sample size: 1,223,856 • Dose ranged: 50,000 IU to 200,000 IU, one study used weekly dose of 3866 • Retinol palmitate was the most commonly used compound • Most of the studies lasted about one year or less and about 11 studies lasted for 5 years
  30. 30. Risk of Bias in the Included Studies
  31. 31. Vitamin A vs. Control: All-Cause Mortality
  32. 32. Diarrhea Mortality: Vitamin A vs. Control
  33. 33. Measles Mortality: Vitamin A vs. Control
  34. 34. LRTI Mortality: Vitamin A vs. Control
  35. 35. Diarrhea Incidence: Vitamin A vs. Control
  36. 36. Measles Incidence: Vitamin A vs. Control
  37. 37. LRTI Incidence: Vitamin A vs. Control
  38. 38. Bitot’s Prevalence: Vitamin A vs. Control
  39. 39. Night Blindness Prevalence: Vitamin A vs. Control
  40. 40. Side Effects: Vomiting
  41. 41. Vitamin A Deficiency
  42. 42. Vitamin A: Serum Retinol Level
  43. 43. GRADE: Summary of Findings Table
  44. 44. GRADE: Summary of Findings Table
  45. 45. GRADE: Summary of Findings Table
  46. 46. Strengths/Limitations • Study included 47 RCT representing 1,223,856 children • Standard methods of Cochrane collaboration were used • Both morbidity and mortality outcomes were assessed • The primary analysis for all-cause mortality: 19 trials and included 1,202,382 children randomized in this review
  47. 47. Strengths/Limitations • Inclusion of a recent large trial from India (DEVTA trial) changed the summary estimate from 24 % to 12 %, but overall results remained statistically significant • Overall, there was substantial heterogeneity in the pooled data and the analysis performed in this review could not fully explain the variation of effect • Growth outcomes were not measured in this review
  48. 48. Implications for Public Health • Vitamin A has a robust effect on prevention of mortality in young children • The World Health Organization recommends vitamin A for children 6 and 59 months of age, in a dose of 100,000 IU for children aged 6 to 12 months and a dose of 200,000 IU for children aged 1 to 5 years, every six months
  49. 49. Implications for Public Health • We suggested to continue this policy and WHO used the first publication of this review to issue its guideline and an update is expected soon based on latest evidence • We, however, acknowledge that synthetic vitamin A supplementation may not be a long term solution and other strategies such as fortification, food distribution programs, and horticultural developments should be encouraged
  50. 50. Take Home Message Vitamin A supplementation in children 6-59 months of age reduces all-cause and diarrhea related mortality and it reduces night blindness and illness due to diarrhea and measles
  51. 51. Acknowledgements Prof. Zulfiqar Ahmed Bhutta: The Hospital for Sick Children, Toronto Dr. Kurt Herzer: John Hopkins’ School of Public Health Dr. Evan Mayo Wilson: John Hopkins’ School of Public Health Dr. Mohammad Yawar Yakoob: Aga Khan University, Pakistan Cochrane Developmental Psychosocial and Learning Problems group (CDPLG): Jo Abbott, Chris Champion, Joanne Wilson, Margaret Anderson and Geraldine Macdonald Cochrane Editorial Unit: Toby Lasserson, Rachel Murphy, and Karla Soares-Weiser World Health Organization: Provided partial funding
  52. 52. Questions?
  53. 53. Additional slides
  54. 54. All-Cause Mortality: Subgroup Analysis: Age
  55. 55. All-Cause Mortality: Subgroup Analysis: Gender
  56. 56. All-Cause Mortality: Funnel Plot
  57. 57. Poll Question #4 The information presented today was helpful A.Strongly agree B.Agree C.Neutral D.Disagree E.Strongly disagree
  58. 58. What can I do now? Visit the website; a repository of over 4,000+ quality-rated systematic reviews related to the effectiveness of public health interventions. Health Evidence™ is FREE to use. Register to receive monthly tailored registry updates AND monthly newsletter to keep you up to date on upcoming events and public health news. Tell your colleagues about Health Evidence™: helping you use best evidence to inform public health practice, program planning, and policy decisions! Follow us @HealthEvidence on Twitter and receive daily public health review- related Tweets, receive information about our monthly webinars, as well as announcements and events relevant to public health. Encourage your organization to use Health Evidence™ to search for and apply quality-rated review level evidence to inform program planning and policy decisions. Contact us to suggest topics or provide feedback. info@healthevidence.org
  59. 59. Poll Question #5 What are your next steps? [Check all that apply] A. Access the full text systematic review B. Access the quality assessment for the review on www.healthevidence.org C. Consider using the evidence D. Tell a colleague about the evidence
  60. 60. Thank you! Contact us: info@healthevidence.org For a copy of the presentation please visit: http://www.healthevidence.org/webinars.aspx

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