Siddhartha Gogia

Neonatal vitamin A supplementation for prevention of mortality and morbidity in infancy: systematic review of randomised controlled trials

Objective To evaluate the effect of neonatal vitamin A supplementation on infant mortality, morbidity and early adverse effects. Design Systematic review, meta-analysis, and meta-regression of randomised controlled trials. Data sources Electronic databases and hand search of reviews; abstracts and proceedings of conferences. Review methods Randomised or quasi-randomised or cluster randomised, placebo controlled trials evaluating the effect of prophylactic, neonatal (<1 month) supplementation with synthetic vitamin A on mortality or morbidity within infancy (<1 year), and early adverse effects (≤7 days). Results The six included trials were from developing countries. There was no convincing evidence of a reduced risk of mortality during infancy (relative risk 0.92, 95% confidence interval 0.75 to 1.12, P=0.393 random effect; I2=54.1%) or of an increase in early adverse effects including bulging fontanelle (1.16, 0.81 to 1.65, P=0.418; I2=65.3%). No variable emerged as a significant predictor of mortality, but data for important risk groups (high maternal night blindness prevalence and low birth weights) were restricted. Limited data (from one to four trials) did not indicate a reduced risk of mortality during the neonatal period (0.90, 0.75 to 1.08, P=0.270; I2=0%), cause specific mortality, common morbidities (diarrhoea and others), and admission to hospital. There was, however, evidence of an increased risk of acute respiratory infection and a reduced risk of clinic visits. Conclusions There is no convincing evidence of a reduced risk of mortality and possibly morbidity or of increased early adverse effects after neonatal supplementation with vitamin A. There is thus no justification for initiating such supplementation as a public health intervention in developing countries for reducing infant mortality and morbidity.

Promoting appropriate management of diarrhea: A systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India

BackgroundScaling up of evidence-based management and prevention of childhood diarrhea is a public health priority in India, and necessitates robust literature review, for advocacy and action.ObjectiveTo identify, synthesize and summarize current evidence to guide scaling up of management of diarrhea among under-five children in India, and identify existing knowledge gaps.MethodsA set of questions pertaining to the management (prevention, treatment, and control) of childhood diarrhea was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps.ResultsChildhood diarrhea is a significant public health problem in India; the point (two-weeks) prevalence is 9–20%. Diarrhea accounts for 14% of the total deaths in under-five children in India. Infants aged 6–24 months are at the highest risk of diarrhea. There is a lack of robust nation-wide data on etiology; rotavirus and diarrheogenic E.coli are the most common organisms identified. The current National Guidelines are sufficient for case-management of childhood diarrhea. Exclusive breastfeeding, handwashing and point-of-use water treatment are effective strategies for prevention of all-cause diarrhea; rotavirus vaccines are efficacious to prevent rotavirus specific diarrhea. ORS and zinc are the mainstay of management during an episode of childhood diarrhea but have low coverage in India due to policy and programmatic barriers, whereas indiscriminate use of antibiotics and other drugs is common. Zinc therapy given during diarrhea can be upscaled through existing infrastructure is introducing the training component and information, education and communication activities.ConclusionThis systematic review summarizes current evidence on childhood diarrhea and provides evidence to inform child health programs in India.

Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomized controlled trials

BACKGROUND Maternal postpartum vitamin A supplementation (VAS) provides an opportunity to improve vitamin A nutriture of breast fed infants in developing countries and can possibly prevent infant mortality and morbidity attributable to vitamin A deficiency. OBJECTIVE To evaluate the effect of maternal postpartum VAS on infant mortality, morbidity and adverse effects. DESIGN Systematic review, meta-analysis and meta-regression of randomized controlled trials. DATA SOURCES Electronic databases and abstracts and proceedings of micronutrient conferences. REVIEW METHODS Randomized or quasi-randomized, placebo-controlled trials evaluating the effect of postpartum, maternal synthetic VAS on mortality or morbidity within infancy (<1 year), or adverse effects. RESULTS The seven included trials were from developing countries. There was no evidence of a reduced risk of mortality during infancy [relative risk (RR) 1.05, 95% confidence interval (CI) 0.92-1.20, P = 0.438; I² = 0%, P = 0.940]. No variable emerged as a significant predictor of mortality but data for high-risk groups (high maternal night blindness prevalence and low birth weights) was restricted. Neonatal mortality data was available from a single study, (RR 1.09, 95% CI 0.88-1.35; P = 0.422). In two trials, there was no evidence of a reduced risk of cause-specific mortality. In one trial, there was no evidence of a decrease in either diarrhoea or acute respiratory infection. No adverse effects were reported in the single relevant trial. CONCLUSIONS There is no evidence of a mortality or morbidity benefit to the infant following postpartum maternal VAS. Only prevention of infant morbidity or mortality would be sufficient justification for initiating this intervention in public health programmes.

Response to the commentary: Postpartum vitamin A supplementation and infant mortality

In response to the commentary on our systematic review, we would like to clarify the following aspects. The intent of our systematic review was to strengthen the evidence base for articulation of appropriate global policy on maternal postpartum vitamin A supplementation (VAS) in developing countries. We therefore evaluated the effect of VAS in postpartum mothers (in any dose), irrespective of antenatal VAS status, on mortality, morbidity and adverse effects in their infants until the age of 1 year. The review was not designed to only specifically determine the effects of maternal VAS in doses recommended by either the WHO or a later technical consultation. The objectives and methodology of our review had been approved after a stringent peer review process. We disagree that the ‘meta-analysis was based on diverse data of limited utility for discerning a mortality impact’. Variation among participants, settings and interventions occurs in most, if not all, systematic reviews. In spite of such clinical diversity, there was no statistical heterogeneity (I1⁄4 0%, P1⁄4 0.9) across trials indicating the consistency in findings for infant mortality. On including a subsequent large trial also, there was no evidence of reduced infant mortality [random effect risk ratio (RR) 1.0, 95% confidence interval (CI) 0.94–1.06, P1⁄4 0.9] or heterogeneity (I1⁄4 0%, P1⁄4 0.9). This evidence from 96203 participants in seven trials was of high quality (further research is very unlikely to change our confidence in the estimate of effect) as per GRADE guidelines recommended by Cochrane collaboration. The review’s methodology and conclusions cannot be discredited on the following two critiques. The report of one trial perceived to be of ‘appropriate sample size’ in ‘an HIV infected population’ pertains to only HIV-negative mothers. Even in trials providing small weekly doses of vitamin A, the cumulative dose was 200 000 IU, equivalent to the mega-dose recommended by the WHO. The later technical consultation states: ‘as an alternative to large-dose supplementation, mothers can receive vitamin A at any time postpartum, given as a low dose not exceeding 10 000 IU per day or 25 000 IU per week’. We reiterate that following maternal postpartum VAS, there is no evidence of mortality (high-quality evidence) or morbidity benefits to the infant; these considerations would not alone be sufficient justification for initiating this intervention in public health programmes. However, policy formulation would be based on deliberation of additional consequences including improvement of maternal and infant vitamin A status, maternal benefits (morbidity or mortality), safety and cost-effectiveness. Further, we clarify the following inconsistencies in referring to our ‘parallel meta-analysis effort’ on neonatal VAS. The intervention in participants was restricted to the neonatal period (<1 month age as per standard international nomenclature) and did not extend into ‘early infancy’ as implied in the commentary. In a post hoc analysis mentioned in the Discussion section, we had found no convincing evidence of reduced mortality during infancy for dosing during the first 48 h after birth (random effect RR 0.89, 95% CI 0.73–1.09, P1⁄4 0.256; I1⁄4 56%). It is inappropriate and premature to contemplate regional newborn VAS or its dovetailing with maternal postpartum VAS. The tendency to influence global policy on the basis of successive subgroup analyses (first 48 h of the neonatal period in participants restricted to a region) needs strong and immediate discouragement. Global policy formulation must await further input from all the four ongoing trials.