vitamin d lecture
Post on 14-Apr-2018
215 Views
Preview:
TRANSCRIPT
-
7/27/2019 Vitamin D Lecture
1/23
Vitamin A:
the enigmatic magic bullet
Betty Kirkwood
Dept of Nutrition & Public Health Intervention Research
Faculty of Epidemiology & Population HealthLSHTM
-
7/27/2019 Vitamin D Lecture
2/23
Vitamin A: An essential micronutrient
Metabolic roles Vision
Maintenance of epithelial cells
Immune system
Growth
Fertility
Clinical deficiency
Nightblindness
Xerophthalmia: Dry eye disease
Blindness
-
7/27/2019 Vitamin D Lecture
3/23
Vitamin A: 2 principal forms
Preformed vitamin A(Retinol)
Only in Animal Sources
Fatty fish liver oils
Meat (lambs liver)
Dairy produce
Breast milk
Pro-vitamin A(-Carotene)
Red & orange fruits &vegetables
Mango/papaya Red palm oil
Carrot
Dark green leafy
vegetables, eg. spinachPro-vitamin A converted
to retinol in 6:1 ratio
Stored in liverCapsules: Single large
dose (200,000 iu) lasts
4-6 months
-
7/27/2019 Vitamin D Lecture
4/23
-
7/27/2019 Vitamin D Lecture
5/23
Vitamin A and child mortality:
controversy in the late 1980s
The Lancet, May 24, 1986
Vitamin A supplements decreasedchildhood mortality by 34% in Sumatra,Indonesia (Al Sommer et al)
This finding is at odds with much of theconventional wisdom on the aetiology of
childhood death in developing countries
(Richard Feachem, Bull Hyg Trop Dis 1986)
-
7/27/2019 Vitamin D Lecture
6/23
Meta-analysis (1993): overall reduction
of 23% in child mortality
Indonesia India Nepal Sudan Ghana
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Aceh
1986
Bogor
1988
Tamil Nadu
1990
Hyderabad
1990
Sarlahi
1991
Jumla
1992
Khartoum
1992
UER
1993
Summary
Beaton etal, 1993
RR(9
5%C
I)
Vitamin A supplementation became key
element of child survival strategies
8 RCTs
GHANA VAST
Impact on mortality, hospital admissions,
clinic attendances & on severity but not on
incidence of diarrhoea
-
7/27/2019 Vitamin D Lecture
7/23
An interesting policy response
World Development Report, 1993Investing in Health
VitaminA supplementation a Best Buy
Linked to first three doses of DPT at 6, 10 and14 weeks of age
WHO/UNICEF planning to recommend
for adoption at EPI Global Advisory
Group meeting in Philipines
BUTtrials demonstrated impact in 6-59
month age range
-
7/27/2019 Vitamin D Lecture
8/23
Meta-analysis from all RCTs
0-5 months RR=0.97 (0.73-1.29)
6-11 months RR=0.69 (0.54-0.90)
Pneumonia & Vitamin A Working Group (Bull WHO)
BUTtrials demonstrated impact in
children aged 6-59 months
-
7/27/2019 Vitamin D Lecture
9/23
EPI- linked Vitamin A supplementation:
RCTs in Ghana, India & PeruDeaths/1000
Maternal DPT1-3 Measles
suppl. & Polio 1-3
Age (months)0
10
20
30
40
50
60
70
80
90
6wk 6mo 9mo 12mo
Control groupVitamin A
WHO/CHD Imm unisat ion-Linked Vitamin A Sup plementat ion Study Grou p
Impact on Infant Mortality Impact on Vitamin A status
% retinol
-
7/27/2019 Vitamin D Lecture
10/23
Nepal trial: VAS of women of
reproductive age
Keith West et al: IVACG 1998 & BMJ 1999
Weekly low dose supplements (of either retinol or
beta-carotene) to all women of childbearing age
No impact on infant mortality BUT44% reductionin pregnancy related mortality(95%CI =16-63%),
P
-
7/27/2019 Vitamin D Lecture
11/23
1. Start implementing right away:
Why waste 10 more years on research as was
done with Vitamin A and child health?
Trial in Nepal shows 44% reduction in
pregnancy-related deaths: TWO views
2. Need to replicate before investing:
Does it really work? If not, we waste moneyand divert resources away from improvingaccess and coverage to EOC
Even if it works, can we translate researchfindings into programmes?
-
7/27/2019 Vitamin D Lecture
12/23
Vitamin A & maternal mortality:
New trials
Ghana: All women childbearing age,
Bangladesh: Pregnant women Indonesia: Multivitamins & pregnant women
-
7/27/2019 Vitamin D Lecture
13/23
Ghana ObaapaVitA trial
Cluster randomised double-blindplacebo controlled trial of weeklyVAS (25,000 IU)
All women aged 15-45 years in 6districts in Brong Ahafo region
4 weekly home surveillance
to monitor pregnancies, births, deaths(women and infants), migration
to distribute capsules
Clusters: Geographically contiguouscompounds of 100-200 women
Additional data collection activities(verbal post-mortems for cause ofdeath, hospital data capture)
IEC Strategy to maximise adherenceto capsules GIS Mapping
-
7/27/2019 Vitamin D Lecture
14/23
ObaapaVitA cluster randomised trial
Dec 2000 Oct 2008
1086 clusters
207,781 women
102,952 pregnancies
96,350 livebirths
683,025 women years
Funded by UK DfID (& USAID)
Vitamin A provided by Roche
-
7/27/2019 Vitamin D Lecture
15/23
Summary of Impact of Weekly
Vitamin A Supplements
Outcome Adjusted RR
Pregnancy-related mortality 0.92 (0.73, 1.17)
Adult female mortality 1.01 (0.93, 1.09)
Hospital morbidity (any of 12) 0.98 (0.89, 1.09)Stillbirths 1.04 (0.96, 1.13)
Perinatal mortality 1.01 (0.94, 1.08)
Neonatal mortality 0.95 (0.87, 1.04)Infant mortality 0.98 (0.91, 1.05)
CONCLUSIVE RESULTS:
NO IMPACT in rural Ghana
-
7/27/2019 Vitamin D Lecture
16/23
Maternal mortality and VAS:
Nepal & Ghana - CONTRASTING FINDINGS
0.2 2
VAS
-carotene
Nepal NNIPS-2
Ghana ObaapaVitA
Bangladesh JiVitA
Indonesia SUMMIT
ALL WOMEN OF REPRODUCTIVE AGE
PREGNANT WOMEN
RR (95%CI)1
Lower maternal mortality in Ghana
377 vs 704 deaths/100,000 pregnancies
Nightblindness:
Rare in Ghana vs 10% pregnant women in Nepal BUT subclinical levels VAD in pregnancy similar: 15%
vs 19%
Child trials: impact seen where largely sub-clinical VAD
-
7/27/2019 Vitamin D Lecture
17/23
0.2 2
VAS
-carotene
Nepal NNIPS-2
Ghana ObaapaVitA
Bangladesh JiVitA
Indonesia SUMMIT
ALL WOMEN OF REPRODUCTIVE AGE
PREGNANT WOMEN
RR (95%CI)1
VAS didnt improve serum retinol in Ghana
Dose recommended as safe for pregnant women
Capsule analysis confirmed stable content in field
IEC approach in Ghana, DOS in Nepal Adherence data suggest Ghanaian women taking
capsules (average 82% over 1 year in serum survey)
In Nepal VAS improved serum retinol, BUT -carotene
didnt
Maternal mortality and VAS:
Nepal & Ghana - CONTRASTING FINDINGS
-
7/27/2019 Vitamin D Lecture
18/23
-
7/27/2019 Vitamin D Lecture
19/23
0.2 2
VAS
-carotene
Nepal NNIPS-2
Ghana ObaapaVitA
Bangladesh JiVitA
Indonesia SUMMIT
ALL WOMEN OF REPRODUCTIVE AGE
PREGNANT WOMEN
RR (95%CI)1
Anomalous finding in Nepal Highest reductions in deaths from injuries & unknown or
uncertain causes
Smaller reductions for obstetric causes or infection
What about deaths unrelated to pregnancy?
Maternal mortality and VAS:
Nepal & Ghana - CONTRASTING FINDINGS
-
7/27/2019 Vitamin D Lecture
20/23
Maternal mortality & VAS:
Summary of evidence
0.2 2
VAS
-carotene
MMN
Nepal NNIPS-2
Ghana ObaapaVitA
Bangladesh JiVitA
Indonesia SUMMIT
ALL WOMEN OF REPRODUCTIVE AGE
PREGNANT WOMEN
RR (95%CI)1
Evidence does not support inclusion of low dose VAS of
women in eithersafe motherhood orchild survivalstrategies
-
7/27/2019 Vitamin D Lecture
21/23
NOTE: Weights are from random effects analysis
.
.
Overall (I-squared = 58.6%, p = 0.005)
Klemm 2008 M
Humprey unpublished M
Rahmathullah 2003 M
Klemm 2008 F
ID
Rahmathullah 2003 F
Benn 2010 M
female
Humphrey 1996 F
Subtotal (I-squared = 45.1%, p = 0.105)
Benn 2010 F
Benn 2008 F
Subtotal (I-squared = 71.4%, p = 0.004)
Study
Benn 2008 M
Humphrey 1996 M
Humprey unpublished F
male
0.93 (0.80, 1.07)
0.89 (0.72, 1.10)
1.19 (1.00, 1.42)
0.70 (0.52, 0.94)
0.81 (0.65, 1.00)
ES (95% CI)
0.87 (0.65, 1.17)
0.74 (0.45, 1.22)
0.84 (0.26, 2.77)
0.98 (0.82, 1.17)
1.42 (0.94, 2.15)
1.39 (0.90, 2.14)
0.84 (0.65, 1.09)
0.84 (0.55, 1.27)
0.15 (0.03, 0.68)
0.93 (0.78, 1.14)
100.00
12.45
13.61
9.91
12.34
Weight
9.97
5.60
1.36
50.62
7.09
6.71
49.38
%
6.99
0.81
13.15
0.93 (0.80, 1.07)
0.89 (0.72, 1.10)
1.19 (1.00, 1.42)
0.70 (0.52, 0.94)
0.81 (0.65, 1.00)
ES (95% CI)
0.87 (0.65, 1.17)
0.74 (0.45, 1.22)
0.84 (0.26, 2.77)
0.98 (0.82, 1.17)
1.42 (0.94, 2.15)
1.39 (0.90, 2.14)
0.84 (0.65, 1.09)
0.84 (0.55, 1.27)
0.15 (0.03, 0.68)
0.93 (0.78, 1.14)
100.00
12.45
13.61
9.91
12.34
Weight
9.97
5.60
1.36
50.62
7.09
6.71
49.38
%
6.99
0.81
13.15
1.03 1 33.3
VAS of newborns:
Another controversial area
NEW TRIALS:Ghana, India, Tanzania (100,000 newborns)
-
7/27/2019 Vitamin D Lecture
22/23
Vitamin A:the enigmatic magic bullet
Vitamin A: key child survival strategy
Saves lives of children aged 6-59 months
Saving lives of infants aged
-
7/27/2019 Vitamin D Lecture
23/23
Vitamin A Research: 24 yearsGhana Health Service/LSHTM collaboration
top related