RESUMO
Inadequate protein intake and lack of micronutrients may affect neurodevelopment in infants. This randomised controlled trial was conducted to measure the effect of two milk-cereal mixes with modest and high amounts of protein and enriched with multiple micronutrients, given between 6 and 12 months, on cognitive, language, motor and behavioural scores at 12 and 24 months of age, compared with no-supplementation. The two supplements were also compared with each other. The study was conducted in urban Delhi, India, and the infants were randomised in a 1:1:1 ratio to the three study groups. At 12 and 24 months of age, 1134 and 1214 children were available, respectively. At 12 months of age, compared with no-supplement group, an increase in the motor scores (mean difference, MD 1·52, 95 % CI: 0·28, 2·75) and a decrease in the infant temperament scores (MD - 2·76, 95 % CI: -4·23, -1·29) in the modest-protein group was observed. Those in the high-protein group had lower socio-emotional scores (MD - 1·40, 95 % CI: -2·43, -0·37) and higher scores on Infant Temperament Scale (MD 2·05, 95 % CI: 0·62, 3·48) when compared with modest-protein group. At 24 months, no significant differences in any of the neurodevelopment scores between the three study groups was found. In conclusion, supplementation with modest amount of protein and multiple micronutrients may lead to short-term small improvements in motor function and infant temperament. There appears no advantage of supplementing with high protein, rather negative effects on infant behaviour were observed.
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Grão Comestível , Leite , Animais , Humanos , Lactente , Suplementos Nutricionais , Índia , Micronutrientes , Pré-EscolarRESUMO
BACKGROUND: Low birth weight (LBW), including preterm birth (PTB) and small for gestational age (SGA), contributes a significant global health burden. We aimed to summarise current evidence on the effect of preconception and periconception interventions on LBW, SGA and PTB. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library and WHO Global Index Medicus for randomised controlled trials and quasi-experimental studies published by 28 November 2020, which assessed interventions delivered in preconception and periconception or preconception and pregnancy. Primary outcomes were LBW, SGA and PTB. Studies were categorised by intervention type and delivery during preconception and periconception or during preconception and pregnancy. Estimates were pooled using fixed-effects or random-effects restricted maximum likelihood method meta-analyses. Quality of evidence for primary outcomes was assessed using the Grades of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We included 58 studies. Twenty-eight studies examined nutrition interventions (primarily micronutrient or food supplementation). Thirty studies (including one reporting a nutrition intervention) provided health interventions (general preconception health, early adverse pregnancy outcome prevention, non-communicable disease and infectious disease prevention and management). One study assessed a social intervention (reproductive planning). Studies varied in terms of specific interventions, including delivery across preconception or pregnancy, resulting in few studies for any single comparison. Overall, the evidence was generally very uncertain regarding the impact of any intervention on LBW, SGA and PTB. Additionally, preconception and periconception nutritional supplementation containing folic acid was associated with reduced risk of birth defects (10 studies, N=3 13 312, risk ratio: 0.37 (95% CI: 0.24 to 0.55), I2: 74.33%). CONCLUSION: We found a paucity of evidence regarding the impact of preconception and periconception interventions on LBW, SGA and PTB. Further research on a wider range of interventions is required to clearly ascertain their potential effectiveness. TRIAL REGISTRATION NUMBER: This review was prospectively registered with PROSPERO (CRD42020220915).
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Nascimento Prematuro , Feminino , Ácido Fólico , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Micronutrientes , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/prevenção & controleRESUMO
OBJECTIVES: To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS: Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS: Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.
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Recém-Nascido de Baixo Peso , Micronutrientes , Criança , Suplementos Nutricionais , Transtornos do Crescimento , Humanos , Lactente , Recém-Nascido , Leite HumanoRESUMO
BACKGROUND: A large proportion of infants in low- and middle-income countries are stunted. These infants are often fed complementary foods that are low-quality, primarily in terms of protein and micronutrients. OBJECTIVES: We aimed to test 2 milk-cereal mixes supplemented with modest and high amounts of protein during 6-12 mo of age, compared with no supplementation, for their effect on length-for-age z score (LAZ) at 12 mo of age. METHODS: Eligible infants (6 mo plus ≤29 d) were randomly assigned to either of the 2 interventions (modest- and high-protein) or a no supplement group. The milk-cereal mixes provided â¼125 kcal, 30%-45% energy from fats, and 80%-100% RDA of multiple micronutrients (MMN). The modest-protein group received 2.5 g protein [protein energy ratio (PER): 8%; 0.75 g from milk source] and the high-protein group received 5.6 g protein (PER: 18%, 1.68 g from milk source). One packet was given daily for 180 d. Counseling on continued breastfeeding and optimal infant-care practices was provided to all. RESULTS: We enrolled 1548 infants (high-protein: n = 512; modest-protein: n = 519; and no supplement: n = 517). Compared with the no supplement group, there was an improvement in LAZ [adjusted mean difference (MD): 0.08; 95% CI: 0.01, 0.15], weight-for-age z score (MD: 0.12; 95% CI: 0.06, 0.19), weight-for-length z score (MD: 0.11; 95% CI: 0.02, 0.19), and midupper arm circumference z score (MD: 0.10; 95% CI: 0.02, 0.18) in the high-protein group at 12 mo of age. No significant differences for these anthropometric indicators were noted between the modest-protein and no supplement groups or between the high- and modest-protein groups. CONCLUSIONS: Cereal mixes with higher amounts of milk-based protein and MMN may lead to improvement in linear growth and other anthropometric indexes in infants, compared with no supplementation.This trial was registered at ctri.nic.in as CTRI/2018/04/012932.
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Desenvolvimento Infantil , Suplementos Nutricionais , Grão Comestível , Fenômenos Fisiológicos da Nutrição do Lactente , Leite , Animais , Antropometria , Proteínas Alimentares/administração & dosagem , Feminino , Transtornos do Crescimento/prevenção & controle , Humanos , Índia , Lactente , Masculino , Micronutrientes/administração & dosagemRESUMO
BACKGROUND: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations. METHODS: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis. FINDINGS: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi. INTERPRETATION: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.
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Nascimento Prematuro , Selênio , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologiaRESUMO
BACKGROUND: In lower-middle-income settings, growth faltering in the first 6 mo of life occurs despite exclusive breastfeeding. OBJECTIVE: The aim was to test the efficacy of an approach to improve the dietary adequacy of mothers during lactation and thus improve the growth of their infants. METHODS: Eligible mother-infant dyads (infants ≤7 d of age) were randomly assigned to either intervention or control groups. Mothers in the intervention group received snacks that were to be consumed daily, which provided 600 kcal of energy-with 25-30% of energy derived from fats (150-180 kcal) and 13% of energy from protein (80 kcal). Micronutrients were supplemented as daily tablets. We provided counseling on breastfeeding and infant-care practices to mothers in both groups. The primary outcome was attained infant length-for-age z scores (LAZ) at 6 mo of age. Secondary outcomes included exclusive breastfeeding proportion reported by the mother, maternal BMI and midupper arm circumference (MUAC), hemoglobin concentrations in mothers and infants, and the proportion of anemic infants at 6 mo of age. RESULTS: We enrolled 816 mother-infant dyads. The intervention did not achieve a significant effect on LAZ at 6 mo (adjusted mean difference: 0.09; 95% CI: -0.03, 0.20). Exclusive breastfeeding at 5 mo was higher (45.1% vs. 34.5%; RR: 1.31; 95% CI: 1.04, 1.64) in the intervention group compared with the controls. There were no significant effects on mean hemoglobin concentration or the proportion of anemic infants at 6 mo of age compared with the control group. We noted significant effects on maternal nutritional status (BMI, MUAC, hemoglobin concentration, and proportion anemic). CONCLUSIONS: Postnatal supplementation of 600 kcal energy, 20 g protein, and multiple micronutrients daily to lactating mothers did not affect infant LAZ at age 6 mo. Such supplementation may improve maternal nutritional status. This trial was registered at Clinical Trials Registry-India as CTRI/2018/04/013095.
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Aleitamento Materno , Desenvolvimento Infantil , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Dieta , Suplementos Nutricionais , Feminino , Humanos , Índia , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Micronutrientes , GravidezRESUMO
OBJECTIVE: Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. DESIGN: Multicentre observational cohort study. SETTING: Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia. PARTICIPANTS: Neonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded. OUTCOME MEASURES: Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies). RESULTS: 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%). CONCLUSIONS: In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.
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Icterícia Neonatal , Adolescente , Adulto , Bangladesh , Criança , Pré-Escolar , Estudos de Coortes , Países em Desenvolvimento , Humanos , Lactente , Recém-Nascido , Icterícia Neonatal/diagnóstico , África do Sul , Adulto JovemRESUMO
BACKGROUND: The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children. METHODS: An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team. DISCUSSION: This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings. TRIAL REGISTRATION: Clinical Trial Registry - India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies.
Assuntos
Prestação Integrada de Cuidados de Saúde , Cuidado do Lactente , Valor Nutritivo , Assistência Perinatal/métodos , Cuidado Pré-Concepcional/métodos , Sistemas de Apoio Psicossocial , Qualidade da Água/normas , Adulto , Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/organização & administração , Saúde Ambiental/métodos , Saúde Ambiental/normas , Feminino , Humanos , Higiene/normas , Índia/epidemiologia , Lactente , Cuidado do Lactente/instrumentação , Cuidado do Lactente/métodos , Recém-Nascido , Masculino , Estado Nutricional , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , População RuralRESUMO
BACKGROUND: Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed. METHODS/DESIGN: The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6-59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration. DISCUSSION: The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6-59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea. TRIAL REGISTRATION NUMBER: NCT03078842. TRIAL STATUS: Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.
RESUMO
OBJECTIVES: Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy. DESIGN: Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices. SETTING: Rural Haryana, North India. PARTICIPANTS: Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life. RESULTS: We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30). CONCLUSIONS: LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life. TRIAL REGISTRATION NUMBER: NCT01138449.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Mortalidade Infantil , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Vitamina A/administração & dosagem , Peso ao Nascer , Análise de Dados , Suplementos Nutricionais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Índia , Lactente , Recém-Nascido , Masculino , População RuralRESUMO
BACKGROUND: Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention. METHODS: Data on immunization status of LBW infants enrolled in an individually randomized, double-masked, placebo-controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s). FINDINGS: Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one-third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32-0.47), Muslim religion (AOR 0.41, 95% CI 0.35-0.48) and age of mother <20 years (AOR 0.62, 95% CI 0.52-0.73) were associated with decreased odds of full immunization. Proportion of infants with delayed vaccination for DPT1 and DPT3 were 52% and 81% respectively. Lowest wealth quintiles (AOR 1.51, 95% CI 1.25-1.82), Muslim religion (AOR 1.41, 95% CI 1.21-1.65), mother aged <20 years (AOR 1.31, 95% CI 1.11-1.53) and birth weight <2000 g (AOR 1.20, 95% CI 1.03-1.40) were associated with higher odds of delayed vaccination for DPT-1. Maternal education (≥12 years of schooling) was associated with high odds of full immunization (AOR 2.39, 95% CI 1.97-2.91) and low odds of delayed vaccination for both DPT-1 (AOR 0.59, 95% CI 0.49-0.73) and DPT-3 (AOR 0.57, 95% CI 0.43-0.76). CONCLUSION: In this population, LBW infants are at a risk of delayed and incomplete immunization and therefore need attention. The risks are even higher in identified subgroups that should specifically be targeted.
Assuntos
Imunização/estatística & dados numéricos , Recém-Nascido de Baixo Peso , População Rural , Feminino , Humanos , Índia , Recém-Nascido , MasculinoRESUMO
High rates of child mortality and lost developmental potential in children under 5 years of age remain important challenges and drivers of inequity in the developing world. Substantive progress has been made toward Millennium Development Goal (MDG) 4 to improve child survival, but as we move into the post-2015 sustainable development agenda, much more work is needed to ensure that all children can realize their full and holistic physical, cognitive, psychological, and socio-emotional development potential. This article presents child survival and development as a continuous and multifaceted process and suggests that a life-course perspective of child development should be at the core of future policy making, programming, and research. We suggest that increased attention to child development, beyond child survival, is key to operationalize the sustainable development goals (SDGs), address inequities, build on the demographic dividend, and maximize gains in human potential. An important step toward implementation will be to increase integration of existing interventions for child survival and child development. Integrated interventions have numerous potential benefits, including optimization of resource use, potential additive impacts across multiple domains of health and development, and opportunity to realize a more holistic approach to client-centered care. However, a notable challenge to integration is the continued division between the health sector and other sectors that support child development. Despite these barriers, empirical evidence is available to suggest that successful multisectoral coordination is feasible and leads to improved short- and long-term outcomes in human, social, and economic development.
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Cuidadores , Serviços de Saúde da Criança/organização & administração , Mortalidade da Criança/tendências , Promoção da Saúde , Formulação de Políticas , Cuidadores/educação , Criança , Desenvolvimento Infantil , Serviços de Saúde da Criança/normas , Pré-Escolar , Promoção da Saúde/organização & administração , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Meio Social , Fatores SocioeconômicosRESUMO
BACKGROUND: Supplementation of vitamin A in children aged 6-59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months). METHODS: We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055. FINDINGS: Between Aug 26, 2010, and March 3, 2013, 31,999 newborn babies were randomly assigned to receive vitamin A (n=15,995) or placebo (n=16,004; 15,428 and 15,464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95-1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90-1·29) and for girls was 1·12 (0·91-1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing. INTERPRETATION: Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation. FUNDING: Bill & Melinda Gates Foundation to WHO.
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Deficiência de Vitamina A/tratamento farmacológico , Vitamina A/análogos & derivados , Vitaminas/administração & dosagem , Administração Oral , Cápsulas , Suplementos Nutricionais , Diterpenos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Ésteres de Retinil , Tanzânia/epidemiologia , Resultado do Tratamento , Vitamina A/administração & dosagem , Deficiência de Vitamina A/mortalidade , Vitamina E/administração & dosagemRESUMO
BACKGROUND: Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age. METHODS: We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220. FINDINGS: Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32]). INTERPRETATION: The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy. FUNDING: Bill & Melinda Gates Foundation to WHO.
Assuntos
Deficiência de Vitamina A/tratamento farmacológico , Vitamina A/análogos & derivados , Vitaminas/administração & dosagem , Administração Oral , Cápsulas , Suplementos Nutricionais , Diterpenos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Índia/epidemiologia , Lactente , Mortalidade Infantil , Recém-Nascido , Masculino , Ésteres de Retinil , Resultado do Tratamento , Vitamina A/administração & dosagem , Deficiência de Vitamina A/mortalidade , Vitamina E/administração & dosagemRESUMO
BACKGROUND: Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana. METHODS: This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055. FINDINGS: We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130). INTERPRETATION: The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana. FUNDING: Bill & Melinda Gates Foundation grant to the WHO.
Assuntos
Deficiência de Vitamina A/tratamento farmacológico , Vitamina A/análogos & derivados , Vitaminas/administração & dosagem , Administração Oral , Suplementos Nutricionais , Diterpenos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Gana/epidemiologia , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Ésteres de Retinil , Resultado do Tratamento , Vitamina A/administração & dosagem , Deficiência de Vitamina A/mortalidade , Vitamina ERESUMO
BACKGROUND: Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status. OBJECTIVE: The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo. DESIGN: Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 mo thereafter. RESULTS: Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models. CONCLUSIONS: Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition.
Assuntos
Desenvolvimento Infantil , Transtornos Cognitivos/etiologia , Deficiência de Ácido Fólico/fisiopatologia , Ácido Fólico/administração & dosagem , Estado Nutricional , Deficiência de Vitamina B 12/fisiopatologia , Vitamina B 12/administração & dosagem , Biomarcadores/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/prevenção & controle , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Feminino , Ácido Fólico/sangue , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/prevenção & controle , Homocisteína/sangue , Humanos , Índia/epidemiologia , Lactente , Masculino , Ácido Metilmalônico/sangue , Neurogênese , Prevalência , Desempenho Psicomotor , Vitamina B 12/sangue , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/epidemiologia , Deficiência de Vitamina B 12/prevenção & controleRESUMO
BACKGROUND: Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo. METHODS/DESIGN: The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation. DISCUSSION: The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.
Assuntos
Serviços de Saúde da Criança , Suplementos Nutricionais , Mortalidade Infantil , Projetos de Pesquisa , Vitamina A/administração & dosagem , Fatores Etários , Método Duplo-Cego , Esquema de Medicação , Gana/epidemiologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Tanzânia/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Serviços de Saúde da Criança/métodos , Proteção da Criança/estatística & dados numéricos , Prestação Integrada de Cuidados de Saúde/métodos , Bem-Estar do Lactente/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde/métodos , Serviços de Saúde da Criança/normas , Serviços de Saúde da Criança/estatística & dados numéricos , Mortalidade da Criança , Pré-Escolar , Agentes Comunitários de Saúde/educação , Agentes Comunitários de Saúde/normas , Agentes Comunitários de Saúde/estatística & dados numéricos , Prestação Integrada de Cuidados de Saúde/normas , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Humanos , Índia , Lactente , Mortalidade Infantil , Recém-Nascido , Análise de SobrevidaRESUMO
OBJECTIVE: To compare the estimated prevalence of malnutrition using the World Health Organization's (WHO) child growth standards versus the National Center for Health Statistics' (NCHS) growth reference, to examine the relationship between exclusive breastfeeding and malnutrition, and to determine the sensitivity and specificity of nutritional status indicators for predicting death during infancy. METHODS: A secondary analysis of data on 9424 mother-infant pairs in Ghana, India and Peru was conducted. Mothers and infants were enrolled in a trial of vitamin A supplementation during which the infants' weight, length and feeding practices were assessed regularly. Malnutrition indicators were determined using WHO and NCHS growth standards. FINDINGS: The prevalence of stunting, wasting and underweight in infants aged < 6 months was higher with WHO than NCHS standards. However, the prevalence of underweight in infants aged 6-12 months was much lower with WHO standards. The duration of exclusive breastfeeding was not associated with malnutrition in the first 6 months of life. In infants aged < 6 months, severe underweight at the first immunization visit as determined using WHO standards had the highest sensitivity (70.2%) and specificity (85.8%) for predicting mortality in India. No indicator was a good predictor in Ghana or Peru. In infants aged 6-12 months, underweight at 6 months had the highest sensitivity and specificity for predicting mortality in Ghana (37.0% and 82.2%, respectively) and Peru (33.3% and 97.9% respectively), while wasting was the best predictor in India (sensitivity: 54.6%; specificity: 85.5%). CONCLUSION: Malnutrition indicators determined using WHO standards were better predictors of mortality than those determined using NCHS standards. No association was found between breastfeeding duration and malnutrition at 6 months. Use of WHO child growth standards highlighted the importance of malnutrition in the first 6 months of life.
Assuntos
Aleitamento Materno , Desenvolvimento Infantil , Transtornos da Nutrição do Lactente/complicações , Transtornos da Nutrição do Lactente/mortalidade , Organização Mundial da Saúde , Peso Corporal , Feminino , Gana/epidemiologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Mães , Peru/epidemiologia , Prevalência , Padrões de Referência , Fatores Socioeconômicos , Fatores de TempoRESUMO
Our objective in this trial was to assess the impact of daily zinc supplementation on growth in young children. A double-blind, randomized, placebo-controlled trial was conducted in New Delhi, India. We enrolled 2482 children aged 6-30 mo who were supplemented daily with placebo or zinc (10 mg elemental zinc to infants and 20 mg to older children) for 4 mo. At enrollment, all children also received a single dose of vitamin A (104.7 micromol for infants and 209.4 micromol for older children). Weight and length were measured at enrollment and 4 mo later. Weekly visits were conducted by field workers to ascertain morbidity in the previous 7 d. Change in length, weight, length-for-age Z-scores (LAZ), and weight-for-length Z-scores (WLZ) after 4 mo of supplementation were assessed in the zinc and placebo groups. After 4 mo of supplementation, the weight and length gains in the 2 groups did not differ and there was no impact on LAZ, weight-for-age, and WLZ in the 2 groups. There was no substantial effect in any of the subgroups defined for age, income, gender, zinc levels in the crude analysis nor after adjusting for age, gender, income, breast-feeding status, and baseline anthropometric status. Despite successful zinc supplementation reflected in increased plasma zinc concentration and a substantially reduced incidence of diarrhea and pneumonia in zinc-supplemented children, the intervention did not have a beneficial effect on growth.