Zinc supplementation for mental and motor development in children.

BACKGROUND: Zinc deficiency is a significant public health problem in low- and middle-income countries. Zinc is essential for the formation and migration of neurons along with the formation of neuronal synapses. Its deficiency could interfere with the formation of neural pathways and with neurotransmission, thus affecting behavior (for example, attention, activity, engagement, temperament) and development (for example, gross and fine motor skills, social skills). Zinc supplementation provided to infants and children is a possible strategy to improve the mental and motor development of infants and children at high risk of zinc deficiency. OBJECTIVES: To assess the effects of zinc supplementation compared to placebo on measures of psychomotor development or cognitive function in children. SEARCH METHODS: We searched MEDLINE, PsycINFO, CINAHL and Latin American Database (LILACS) on 1 December 2011. We searched EMBASE and CENTRAL 2011 Issue 12 on 19 January 2012. We searched Dissertation Abstracts International and the metaRegister of Controlled Trials on 30 November 2011. SELECTION CRITERIA: Randomized or quasi-randomized placebo-controlled trials involving synthetic zinc supplementation provided to infants or children (less than five years of age) were eligible. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, selected studies, assessed the studies for their risk of bias and extracted data. MAIN RESULTS: We included 13 trials in this review.Eight studies reported data on the Bayley Scales of Infant Development (BSID) in 2134 participants. We combined the data in a meta-analysis to assess the effect on development as measured by the Mental Development Index (MDI) and Psychomotor Development Index (PDI). There was no significant effect of zinc supplementation: the mean difference between the zinc supplementation and placebo groups on the MDI was -0.50 (95% confidence interval (CI) -2.06 to 1.06; P = 0.53; I(2) = 70%) and the mean difference between the groups for the PDI was 1.54 (95% CI -2.26 to 5.34; P = 0.43; I(2) = 93%). Most studies had low or unclear risk of bias but there was significant heterogeneity, which was not adequately explained by our subgroup analyses. The overall quality of evidence was considered 'moderate'.Two trials provided data on motor milestone attainment. There was no significant difference in the time to attainment of milestones between the placebo group and the zinc supplementation group in either of the studies.No study provided data on cognition score or intelligence quotient (IQ) or on adverse effects of zinc supplementation. AUTHORS' CONCLUSIONS: There is no convincing evidence that zinc supplementation to infants or children results in improved motor or mental development.

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

BACKGROUND: Scaling 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. OBJECTIVE: To 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. METHODS: A 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. RESULTS: Childhood diarrhea is a significant public health problem in India; the point (two weeks) prevalence is 9 to 20%. Diarrhea accounts for 14% of the total deaths in under-five children in India. Infants aged 6 to 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. CONCLUSION: This systematic review summarizes current evidence on childhood diarrhea and provides evidence to inform child health programs in India.

Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less.

BACKGROUND: Vitamin A deficiency is a significant public health problem in low and middle income countries. Vitamin A supplementation (VAS) provided to lactating postpartum mothers or to infants less than six months of age are two possible strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity. OBJECTIVES: To evaluate the effect of:1. VAS in postpartum breast feeding mothers in low and middle income countries, irrespective of antenatal VAS status, on mortality, morbidity and adverse effects in their infants up until the age of one year.2. VAS initiated in the first half of infancy (< 6 months of age) in low and middle income countries, irrespective of maternal antenatal or postnatal VAS status, on mortality, morbidity and adverse effects up until the age of one year. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), EMBASE, MEDLINE, clinical trials websites, conference proceedings, donor agencies, 'experts' and researchers (up to October 15, 2010). SELECTION CRITERIA: Randomized or quasi-randomised, individually or cluster randomised, placebo controlled trials involving synthetic VAS provided to the postpartum mothers or their infants up to the age of six months were eligible. DATA COLLECTION AND ANALYSIS: Two review authors assessed the studies for their risk of bias and collected data on outcomes. MAIN RESULTS: Of the 18 included studies, eight provided information on maternal VAS and 15 on infant VAS.For maternal VAS, there was no evidence of a reduced risk of mortality of their babies during infancy (96,203 participants, seven studies, high quality evidence; random-effects model RR 1.00, 95% CI 0.94 to 1.06, P = 0.9; test of heterogeneity I(2) = 0%, P = 0.9) or in the neonatal period (moderate quality evidence); nor of morbidities (very low quality evidence).  For infant VAS, there was no evidence of a reduced risk of mortality during infancy (59,402 participants, nine studies, moderate quality evidence; random-effects model RR 0.97, 0.83 to 1.12, P = 0.65; test of heterogeneity I(2) = 49%, P = 0.05) or in the neonatal period, nor morbidities (low quality evidence), but an increased risk of bulging fontanelle (32,978 participants, 10 studies, low quality evidence; random-effects model RR 1.55, 1.05 to 2.28, P = 0.03; test of heterogeneity I(2) = 68%, P = 0.0009). AUTHORS' CONCLUSIONS: There is no convincing evidence that either maternal postpartum or infant vitamin A supplementation results in a reduction in infant mortality or morbidity in low and middle income countries.

Community based newborn care: a systematic review and metaanalysis of evidence: UNICEF-PHFI series on newborn and child health, India.

BACKGROUND: The neonatal mortality rate (NMR) in India has remained virtually unchanged in the last 5 years. To achieve the Millennium Development Goal (MDG) 4 on child mortality (two thirds reduction from 1990 to 2015), it is essential to reduce NMR. A systematic review of the evidence on community-based intervention packages to reduce NMR is essential for advocacy and action to reach MDG-4. OBJECTIVE: To assess the effect of community based neonatal care by community health workers (CHWs) on NMR in resource-limited settings. DESIGN: Systematic review and meta-analysis of controlled trials. DATA SOURCES: Electronic databases and hand search of reviews, and abstracts and proceedings of conferences. RESULTS: A total of 13 controlled trials involving about 192000 births were included in this systematic review. Community based neonatal care by CHWs was associated with reduced neonatal mortality in resource-limited settings [RR=0.73 (0.65 to 0.83); P<0.0001]. The identified studies were a heterogeneous mix with respect to the extent and quality of community based neonatal care provided and the characteristics of the CHWs delivering the intervention. There was no consistent effect of training duration of the health workers, type of intervention (home visitation versus community participatory action and learning), number of home visits done by CHWs, and provision of only preventive versus both preventive and therapeutic care. Limited data suggests that the ideal time for the first postnatal visit is the first two days of life. The interventions are highly effective when baseline NMR is above 50/1000 live births [RR=0.64(0.54 to 0.77)]. The interventions show a significant decrease in efficacy as the NMR drops below 50/1000 live births [RR=0.85 (0.73 to 0.99)], however is still substantial. NMR gains from home visitation approach are going to materialize only in the presence of high program coverage of 50% or more. CONCLUSION: A significant decrease in NMR is possible by providing community based neonatal care in areas with high NMR by community health workers with a modest training duration and ensuring high program coverage with home visitation on the first two days of life.

UNICEF-PHFI Series on newborn and child health, India: methodology for systematic reviews on child health priorities for advocacy and action.

India is committed to reducing childhood mortality and morbidity. This requires evidence-based policy and practice in the realm of public health. This in turn necessitates advocacy and action (among all stakeholders), focused on locally relevant issues. A collaboration to work towards this goal was forged between the Public Health Foundation of India (PHFI), United Nations International Childrens Emergency Fund (UNICEF), India; and a team of independent researchers. As a first step, a systematic review of literature on four priority areas of newborn care (community based interventions) and child health (acute respiratory infection, diarrheal disease, anemia), was undertaken to address important issues including epidemiology, interventions for management, and operational issues of planning, implementing, and measuring actions at a programmatic level. This paper describes the development of the methodology for undertaking these systematic reviews including the process for framing of research questions, building a research team, and executing the systematic review (literature search strategy, data extraction, analysis, and reporting). The challenges associated with ensuring robust methodology, are also described.

Acute respiratory infection and pneumonia in India: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India.

BACKGROUND: Scaling up of evidence based management of childhood acute respiratory infection/pneumonia, is a public health priority in India, and necessitates robust literature review, for advocacy and action. OBJECTIVE: To identify, synthesize and summarize current evidence to guide scaling up of management of childhood acute respiratory infection/pneumonia in India, and identify existing knowledge gaps. METHODS: A set of ten questions pertaining to the management (prevention, treatment, and control) of childhood ARI/pneumonia 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. RESULTS: Childhood ARI/pneumonia is a significant public health problem in India, although robust epidemiological data is not available on its incidence. Mortality due to pneumonia accounts for approximately one-fourth of the total deaths in under five children, in India. Pneumonia affects children irrespective of socioeconomic status; with higher risk among young infants, malnourished children, non-exclusively breastfed children and those with exposure to solid fuel use. There is lack of robust nation-wide data on etiology; bacteria (including Pneumococcus, H. influenzae, S. aureus and Gram negative bacilli), viruses (especially RSV) and Mycoplasma, are the common organisms identified. In-vitro resistance to cotrimoxazole is high. Wheezing is commonly associated with ARI/pneumonia in children, but difficult to appreciate without auscultation. The current WHO guidelines as modified by IndiaCLEN Task force on Penumonia (2010), are sufficient for case-management of childhood pneumonia. Other important interventions to prevent mortality are oxygen therapy for those with severe or very severe pneumonia and measles vaccination for all infants. There is insufficient evidence for protective or curative effect of vitamin A; zinc supplementation could be beneficial to prevent pneumonia, although it has no therapeutic benefit. There is insufficient evidence on potential effectiveness and cost-effectiveness of Hib and Pneumococcal vaccines on reduction of ARI specific mortality. Case-finding and community-based management are effective management strategies, but have low coverage in India due to policy and programmatic barriers. There is a significant gap in the utilization of existing services, provider practices as well as family practices in seeking care. CONCLUSION: The systematic review summarizes current evidence on childhood ARI and pneumonia management and provides evidence to inform child health programs in India.

Home visits by community health workers to prevent neonatal deaths in developing countries: a systematic review.

OBJECTIVE: To determine whether home visits for neonatal care by community health workers can reduce infant and neonatal deaths and stillbirths in resource-limited settings. METHODS: We conducted a systematic review up to 2008 of controlled trials comparing various intervention packages, one of them being home visits for neonatal care by community health workers. We performed meta-analysis to calculate the pooled risk of outcomes. FINDINGS: Five trials, all from south Asia, satisfied the inclusion criteria. The intervention packages included in them comprised antenatal home visits (all trials), home visits during the neonatal period (all trials), home-based treatment for illness (3 trials) and community mobilization efforts (4 trials). Meta-analysis showed a reduced risk of neonatal death (relative risk, RR: 0.62; 95% confidence interval, CI: 0.44-0.87) and stillbirth (RR: 0.76; 95% CI: 0.65-0.89), and a significant improvement in antenatal and neonatal practice indicators (> 1 antenatal check-up, 2 doses of maternal tetanus toxoid, clean umbilical cord care, early breastfeeding and delayed bathing). Only one trial recorded infant deaths (RR: 0.41; 0.30-0.57). Subgroup analyses suggested a greater survival benefit when home visit coverage was ≥ 50% (P < 0.001) and when both preventive and curative interventions (injectable antibiotics) were conducted (P = 0.088). CONCLUSION: Home visits for antenatal and neonatal care, together with community mobilization activities, are associated with reduced neonatal mortality and stillbirths in southern Asian settings with high neonatal mortality and poor access to facility-based health care.

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.

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 (

Albright's hereditary osteodystrophy.

Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. Pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.

Pantothenate kinase associated neurodegeneration (Hallervorden-Spatz syndrome).

Hallervorden-Spatz syndrome is a rare autosomal recessive hereditary condition characterized by early onset of progressive movement alteration that include dystonia, rigidity and choreoathetosis usually associated with pyramidal signs and mental deterioration. We report two sisters where diagnosis was missed till MRI showed classic imaging findings. Mutation analysis in one, revealed homozygous mutations in the PANK 2 gene. The need for clinical recognition of this entity and differentiation of this form from other static and progressive neurological illnesses is emphasized.

Pantothenate kinase associated neurodegeneration (Hallervorden - Spatz syndrome).

Hallervorden-Spatz syndrome is a rare autosomal recessive hereditary condition characterized by early onset of progressive movement alteration that include dystonia, rigidity and choreoathetosis usually associated with pyramidal signs and mental deterioration. We report two sisters where diagnosis was missed till MRI showed classic imaging findings. Mutation analysis in one, revealed homozygous mutations in the PANK 2 gene. The need for clinical recognition of this entity and differentiation of this form from other static and progressive neurological illnesses is emphasized.

Neurocysticercosis in children: clinical findings and response to albendazole therapy in a randomized, double-blind, placebo-controlled trial in newly diagnosed cases.

The clinical findings of neurocysticercosis, diagnosed primarily on the basis of computed tomography (CT), and response to albendazole therapy in a randomized, double-blind, placebo-controlled trial were studied in 72 newly diagnosed children aged 1.5-12 years admitted to hospital in New Delhi, India, during March to July 2000. The lesions by initial CT were mostly single with perilesional oedema, and were located in the parietal lobes. The most common clinical finding was partial seizure (79.2%). The outcome of the albendazole trial was assessed through changes in CT lesions and status of seizure after 6 months of follow-up; about 55% of the lesions had disappeared and about 80% of the children were seizure-free. The frequency of healing of CT lesions in the albendazole-treated group and placebo group was 54.2% and 55.2%, respectively, and the frequency of a seizure-free state in the albendazole-treated group and placebo group was 87.5% and 77.5%, respectively; the differences were not statistically significant. Changes in lesions by CT and the recurrence of seizures after 6 months of follow-up were not related to the number of lesions by initial CT and albendazole was not beneficial in neurocysticercosis in children with ring-enhancing lesions in CT.