Potential interventions for the prevention of childhood pneumonia in developing countries: a meta-analysis of data from field trials to assess the impact of vitamin A supplementation on pneumonia morbidity and mortality. The Vitamin A and Pneumonia Working Group.

Reported are the results of a meta-analysis (12 large-scale field trials in seven countries) of the impact of vitamin A supplementation on pneumonia morbidity and mortality, undertaken as part of a wider review process of a range of possible potential interventions for the prevention of childhood pneumonia. The summary estimate of the relative risk for the impact of vitamin A supplementation on pneumonia incidence was 0.95 (95% confidence interval (CI) = 0.89, 1.01), and for pneumonia mortality, 0.98 (95% CI = 0.75, 1.28). This is in marked contrast to the substantial impact of vitamin A supplementation on all-cause mortality (combined rate ratio (RR) = 0.77, 95% CI = 0.71, 0.84), and on diarrhoea-specific and measles-specific mortality. There was no evidence for a differential impact on pneumonia mortality by age. Since the majority of pneumonia deaths occur in the first year of life, we complemented the paucity of data on pneumonia-specific mortality among this age group with a detailed examination of all-cause mortality among infants. The mortality reduction in the 6-11 month age group was consistent with that observed for older age groups (RR = 0.69; 95% CI = 0.54, 0.90), but there was no reduction for 0-5 month-olds (RR = 0.97; 95% CI = 0.73, 1.29)

Cost-Effectiveness of “Golden Mustard” for Treating Vitamin A Deficiency in India

BACKGROUND: Vitamin A deficiency (VAD) is an important nutritional problem in India, resulting in an increased risk of severe morbidity and mortality. Periodic, high-dose vitamin A supplementation is the WHO-recommended method to prevent VAD, since a single dose can compensate for reduced dietary intake or increased need over a period of several months. However, in India only 34 percent of targeted children currently receive the two doses per year, and new strategies are urgently needed. METHODOLOGY: Recent advancements in biotechnology permit alternative strategies for increasing the vitamin A content of common foods. Mustard (Brassica juncea), which is consumed widely in the form of oil by VAD populations, can be genetically modified to express high levels of beta-carotene, a precursor to vitamin A. Using estimates for consumption, we compare predicted costs and benefits of genetically modified (GM) fortification of mustard seed with high-dose vitamin A supplementation and industrial fortification of mustard oil during processing to alleviate VAD by calculating the avertable health burden in terms of disability-adjusted life years (DALY). PRINCIPAL FINDINGS: We found that all three interventions potentially avert significant numbers of DALYs and deaths. Expanding vitamin A supplementation to all areas was the least costly intervention, at $23-$50 per DALY averted and $1,000-$6,100 per death averted, though cost-effectiveness varied with prevailing health subcenter coverage. GM fortification could avert 5 million-6 million more DALYs and 8,000-46,000 more deaths, mainly because it would benefit the entire population and not just children. However, the costs associated with GM fortification were nearly five times those of supplementation. Industrial fortification was dominated by both GM fortification and supplementation. The cost-effectiveness ratio of each intervention decreased with the prevalence of VAD and was sensitive to the efficacy rate of averted mortality. CONCLUSIONS: Although supplementation is the least costly intervention, our findings also indicate that GM fortification could reduce the VAD disease burden to a substantially greater degree because of its wider reach. Given the difficulties in expanding supplementation to areas without health subcenters, GM fortification of mustard seed is an attractive alternative, and further exploration of this technology is warranted

Newborn Vitamin A Dosing Reduces the Case Fatality but Not Incidence of Common Childhood Morbidities in South India

Vitamin A supplementation reduces mortality in young children in areas of endemic vitamin A deficiency. However, it has no impact on the incidence of common morbidities. This discrepancy has been explained by an impact on case fatality, although with the exception of hospitalized measles cases, there is little direct evidence to support this hypothesis. We assessed the impact of newborn dosing with vitamin A on the incidence and case fatality of common childhood morbidities in early infancy in a community-based, randomized trial in South India. Morbidity for each day in the previous 2 wk was assessed for the first 6 mo of life. A total of 11,619 live-born infants were enrolled and randomized to receive either 48,000 IU (50.4 μmol retinol) of oral vitamin A or placebo following delivery. There was no difference between treatment groups in the incidence of acute or chronic diarrhea, dysentery, or fever but a small increased incidence of acute respiratory illness (ARI). Case fatality for diarrhea and fever were significantly reduced in the vitamin A group compared with placebo (relative case fatality [95% CI] of 0.50 [0.27, 0.90] and 0.60 [0.40, 0.88], respectively). There was a trend in reduction of case fatality for various definitions of ARI, but the evidence for this effect was modest. Survival analysis among those with morbid episodes confirmed the case fatality analysis. This trial demonstrated that the reduction in overall mortality due to newborn vitamin A dosing was driven primarily by a reduction in case fatality among infants. © 2007 American Society for Nutrition

Maternal night blindness during pregnancy is associated with low birthweight, morbidity, and poor growth in South India

Maternal night blindness is common during pregnancy in many developing countries. Previous studies have demonstrated important consequences of maternal night blindness during pregnancy on the health of the mother and newborn infant. We compared birthweight, 6-mo infant mortality, morbidity, and growth among infants of women who did and did not report a history of night blindness from a community-based, randomized trial of newborn vitamin A supplementation in south India. Birthweight was measured within 72 h of delivery. Infants were followed until 6 mo of age for mortality and morbidity was assessed at household visits every 2 wk. Anthropometry was assessed at 6 mo of age. A total of 12,829 live-born infants were included, 680 of whom were infants of mothers with night blindness during the index pregnancy. Maternal night blindness was associated with an increased risk of low birthweight in a dose-dependent fashion based on birthweight cut-offs: \u3c2500 g, adjusted relative risk (RR) = 1.13 (95% CI = 1.01, 1.26); \u3c2000 g, adjusted RR = 1.70 (95% CI = 1.27, 2.26); \u3c1500 g, adjusted RR = 3.38 (95% CI = 1.18, 6.33); with an increased risk of diarrhea (adjusted RR = 1.16, 95% CI = 1.03, 1.30), dysentery (adjusted RR = 1.25, 95% CI = 1.03, 1.53), acute respiratory illness (adjusted RR = 1.32, 95% CI = 1.21, 1.44), and poor growth at 6 mo; underweight (adjusted RR = 1.14, 95% CI = 1.02, 1.26), stunting (adjusted RR = 1.19, 95% CI = 1.05, 1.34). Maternal night blindness was not associated with 6-mo infant mortality or wasting at 6 mo. This study demonstrates that there are important consequences to the infant of maternal vitamin A deficiency during pregnancy. © 2008 American Society for Nutrition

Newborn vitamin A dosing reduces the case fatality but not incidence of common childhood morbidities in South India

Vitamin A supplementation reduces mortality in young children in areas of endemic vitamin A deficiency. However, it has no impact on the incidence of common morbidities. This discrepancy has been explained by an impact on case fatality, although with the exception of hospitalized measles cases, there is little direct evidence to support this hypothesis. We assessed the impact of newborn dosing with vitamin A on the incidence and case fatality of common childhood morbidities in early infancy in a community-based, randomized trial in South India. Morbidity for each day in the previous 2 wk was assessed for the first 6 mo of life. A total of 11,619 live-born infants were enrolled and randomized to receive either 48,000 IU (50.4 μmol retinol) of oral vitamin A or placebo following delivery. There was no difference between treatment groups in the incidence of acute or chronic diarrhea, dysentery, or fever but a small increased incidence of acute respiratory illness (ARI). Case fatality for diarrhea and fever were significantly reduced in the vitamin A group compared with placebo (relative case fatality [95% CI] of 0.50 [0.27, 0.90] and 0.60 [0.40, 0.88], respectively). There was a trend in reduction of case fatality for various definitions of ARI, but the evidence for this effect was modest. Survival analysis among those with morbid episodes confirmed the case fatality analysis. This trial demonstrated that the reduction in overall mortality due to newborn vitamin A dosing was driven primarily by a reduction in case fatality among infants. © 2007 American Society for Nutrition

Exposure to indoor biomass fuel and tobacco smoke and risk of adverse reproductive outcomes, mortality, respiratory morbidity and growth among newborn infants in south India

Background: Exposure to indoor air pollution due to open burning of biomass fuel is common in low- and middle-income countries. Previous studies linked this exposure to an increased risk of respiratory illness, low birth weight (LBW) and other disorders. We assessed the association between exposure to biomass fuel sources and second-hand tobacco smoke (SHTS) in the home and adverse health outcomes in early infancy in a population in rural south India. Methods: A population-based cohort of newborns was followed from birth through 6 months. Household characteristics were assessed during an enrolment interview including the primary type of cooking fuel and smoking behaviour of household residents. Follow-up visits for morbidity were carried out every 2 weeks after delivery. Infants were discharged at 6 months when anthropometric measurements were collected. Results: 11 728 live-born infants were enrolled and followed, of whom 92.3% resided in households that used wood and/or dung as a primary source of fuel. Exposure to biomass fuel was associated with an adjusted 49% increased risk of LBW, a 34% increased incidence of respiratory illness and a 21% increased risk of 6-month infant mortality. Exposed infants also had 45 and 30% increased risks of underweight and stunting at 6 months. SHTS exposure was also associated with these adverse health outcomes except for attained growth. Conclusions: Open burning of biomass fuel in the home is associated with significant health risks to the newborn child and young infant. Community-based trials are needed to clarify causal connections and identify effective approaches to reduce this burden of illnesses. © The Author 2009; all rights reserved

Breast-feeding initiation time and neonatal mortality risk among newborns in South India

Objective: To examine the association between breast-feeding initiation time and neonatal mortality in India, where breast-feeding initiation varies widely from region to region. Study Design: Data were collected as part of a community-based, randomized, placebo-controlled trial of the impact of vitamin A supplementation in rural villages of Tamil Nadu, India. Multivariate binomial regression analysis was used to estimate the association between neonatal mortality and breast-feeding initiation time (\u3c12 h, 12 to 24 h, \u3e24 h) among infants surviving a minimum of 48 h. Result: Among 10 464 newborns, 82.1% were first breast-fed before 12 h, 13.8% were breast-fed between 12 and 24 h, and 4.1% were breast-fed after 24 h. After adjusting for birth weight, gestational age and other covariates, late initiators (\u3e24 h) were at ∼78% higher risk of death (relative risk=1.78 (95% confidence interval (CI)=1.03 to 3.10)). There was no difference in mortality risk when comparing babies fed in the first 12 h compared with the second 12 h after birth. Conclusion: Late (\u3e24 h) initiation of breast-feeding is associated with a higher risk of neonatal mortality in Tamil Nadu. Emphasis on breast-feeding promotion programs in low-resource settings of India where early initiation is low could significantly reduce neonatal mortality. © 2011 Nature America, Inc. All rights reserved

A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol.

BACKGROUND: Vitamin A supplementation significantly reduces all-cause mortality when given between 6-59 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization. METHODS/DESIGN: In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother-infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (Treg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses. DISCUSSION: Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy. TRIAL REGISTRATION: clinicaltrials.gov NCT01476358