Early neonatal vitamin A supplementation and infant mortality: An individual participant data meta-analysis of randomised controlled trials

Background: Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.Methods: Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.Findings Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol 32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.Conclusion NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial

Typhoid and paratyphoid fever

Typhoid fever is estimated to have caused 21·6 million illnesses and 216 500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings

Limited Progress in Increasing Coverage of Neonatal and Child-health Interventions in Africa and Asia

The study was conducted to analyze recent trends in the coverage of selected child-survival interventions. A systematic analysis of the coverage of six key child-health interventions in 29 African and Asian countries that had two recent demographic and health surveys—the latest one carried out in 2001 onwards and the immediately preceding survey conducted after 1990—was undertaken. A regression model was used for examining the relationship between the changes in the coverage of interventions and the changes in rates of mortality among children aged less than five years (under-five mortality). A limited increase in the coverage of key child-health interventions occurred in the past 5–10 years in these 29 countries in sub-Saharan Africa and Asia. More than half of the countries had no significant improvement or a significant reduction in the coverage of oral rehydration therapy (ORT) for diarrhoea (17/29) and care-seeking for acute respiratory infection (ARI) (16/29). Results of multivariate analysis revealed that increases in the coverage of early initiation of breastfeeding, ORT for diarrhoea, and care-seeking for ARI were significantly associated with reductions in under-five mortality. The results of this analysis should serve as a wake-up call for policy-makers and programme managers in countries, donors, and international agencies to accelerate efforts to increase the coverage of key child-survival interventions. The following three main actions are proposed: setting of the clear target; mobilization of resources for increasing skilled birth attendants and health workers trained in integrated management of childhood illness; and implementation of community-based approaches

Impact of zinc supplementation on mental and psychomotor scores of children aged 12 to 18 months: a randomized, double-blind trial

Objective: To evaluate the effect of zinc supplementation on mental and psychomotor scores in children aged 12 to 18 months. Study design: In this double-blind, randomized, placebo-controlled trial, children aged 6 to 30 months received daily elemental zinc (10 mg for infants and 20 mg for others) or placebo for 4 months. Bayley Scales of Infant Development II were used for development assessment in the 12- to 18-month subgroup at enrollment and the end of the study. Results: At the end of the study, the adjusted mean mental (P = 0.36) and psychomotor (P = 0.28) index scores were similar in the intervention and control groups. In a multivariate model, the baseline mental development index score was positively associated with the mother's schooling, the child's height for age, packed cell volumes, hospital birth, and attendance at a day care center, and was negatively associated with the child's age. Breastfeeding, the child's weight for height, and packed cell volumes were positively associated with the baseline psychomotor index score. Conclusion: Zinc supplementation did not affect the mental or psychomotor development index scores in a setting in which zinc deficiency is common

Breast-feeding status alters the effect of vitamin A treatment during acute diarrhea in children

Vitamin A administration in children reduces the incidence of severe diarrhea during the subsequent few months. We therefore examined the effect of treatment with vitamin A during acute diarrhea on the episode duration and severity. In a double-blind controlled field trial, 900 children 1 to 5 y of age with acute diarrhea of ≤ 7 d duration were randomly assigned to receive vitamin A (60 mg) or a placebo. Children were followed up at home every alternate day until they recovered from the diarrheal episode. In all study children, those treated with vitamin A had a significantly lower risk of persistent diarrhea [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.07-0.97], but there was no effect on the mean diarrheal duration or the mean stool frequency. In the subgroup of children who were not breast-fed, the mean diarrheal duration [ratio of geometric means (GM) 0.84, 95% CI 0.72-0.97], mean number of stools passed after the intervention (ratio of GM 0.73, 95% CI 0.56-0.95), the proportion of episodes lasting ≥ 14 d (P = 0.002) and the percentage of children who passed watery stools on any study day (OR 0.40, 95% CI 0.21-0.77) were significantly lower in those treated with vitamin A. We conclude that administration of vitamin A during acute diarrhea may reduce the severity of the episode and the risk of persistent diarrhea in non-breast-fed children. Similar benefit was not seen in breast-fed children

Standards for CHERG reviews of intervention effects on child survival

Background The Lives Saved Tool (LiST) uses estimates of the effects of interventions on cause-specific child mortality as a basis for generating projections of child lives that could be saved by increasing coverage of effective interventions. Estimates of intervention effects are an essential element of LiST, and need to reflect the best available scientific evidence. This article describes the guidelines developed by the Child Health Epidemiology Reference Group (CHERG) that are applied by scientists conducting reviews of intervention effects for use in LiST. Methods The guidelines build on and extend those developed by the Cochrane Collaboration and the Working Group for Grading of Recommendations Assessment, Development and Evaluation (GRADE). They reflect the experience gained by the CHERG intervention review groups in conducting the reviews published in this volume, and will continue to be refined through future reviews. Presentation of the guidelines Expected products and guidelines are described for six steps in the CHERG intervention review process: (i) defining the scope of the review; (ii) conducting the literature search; (iii) extracting information from individual studies; (iv) assessing and summarizing the evidence; (v) translating the evidence into estimates of intervention effects and (vi) presenting the results. Conclusions The CHERG intervention reviews represent an ambitious effort to summarize existing evidence and use it as the basis for supporting sound public health decision making through LiST. These efforts will continue, and a similar process is now under way to assess intervention effects for reducing maternal mortalit

Assessment of Implementation of Integrated Management of Neonatal and Childhood Illness in India

At the current rate of decline in infant mortality, India is unlikely to achieve the Millennium Development Goal on child survival. Integrated Management of Neonatal and Childhood Illness (IMNCI), adapted from the global Integrated Management of Childhood Illness to enhance the focus on newborns and on community health workers, is the central strategy within the National Reproductive and Child Health Programme to address high infant mortality. This paper assessed the progress of IMNCI in India, identified the programme bottlenecks, and also assessed the effect on coverage of key newborn and childcare practices. Programme data were analyzed to ascertain the implementation status; rapid programme assessment was conducted for identifying the programme bottlenecks; and results of analysis of two rounds of district-level household surveys were used for comparing the change in the coverage of child-health interventions in IMNCI and control districts. More than 200,000 community health workers and first-level healthcare providers were trained during 2005-2009 at a variable pace across 223 districts. Of the reported births (n=1,102,573), 65.5% were visited by a trained worker within 24 hours, and 63.1% were visited three times within 10 days. Poor supervision and inadequate essential supplies affected the performance of trained workers. During 2004-2008, 12 early-implementing districts had covered most key newborn and child practice indicators compared to the control districts; however, the difference was significant only for care-seeking for acute respiratory infection (net difference: 17.8%; 95% confidence interval 2.3-33.2, p<0.026). Based on the early experience of IMNCI implementation in different states of India, measures need to be taken to improve supportive supervision, availability of essential supplies, and monitoring of the programme if the strategy has to translate into improved child survival in India

Vitamin A Administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1.18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p<0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvemen

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p &lt; 0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvement