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Sahin S, Sari FN, Bidev D, Bozkurt O, Dizdar EA, Oguz SS. Zinc Supplementation in Very Low Birth Weight Infants: A Randomized Controlled Trial. Am J Perinatol 2024; 41:e3107-e3114. [PMID: 37939725 DOI: 10.1055/s-0043-1776762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
OBJECTIVE Preterm infants have high zinc (Zn) requirements and are generally believed to be in a negative Zn balance in the early period of life. In this study, we aimed to investigate the effect of high-dose Zn supplementation in very low birth weight (VLBW: infants with birth weight < 1.5 kg) infants on feeding intolerance and development of mortality and/or morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS). STUDY DESIGN This is a prospective randomized trial. VLBW preterm infants with gestational age of <32 weeks were randomly allocated on the seventh day of life to receive extra amount of supplemental Zn along with the enteral feedings (9 + 3 mg), besides regular low-dose supplementation (3 mg), from enrollment until discharge. Outcome measures were feeding intolerance, NEC (stage ≥ 2), LOS, and mortality. RESULTS A total of 195 infants (97 from study group and 98 from control group) were analyzed. A total of 46 (47.4%) infants in the study group and 64 (65.3%) infants in the control group ended up with feeding intolerance (p = 0.012). NEC was observed in 11 infants (11.2%) in the control group and only 1 infant (1%) in the study group (p = 0.003). There was a negative correlation between high-dose Zn supplementation and number of culture-proven LOS episodes (p = 0.041). This significance was also present for clinical sepsis, being higher in the control group (p = 0.029). No relationship between high-dose Zn supplementation and mortality and other morbidities (hemodynamically significant patent ductus arteriosus, bronchopulmonary dysplasia, retinopathy of prematurity, and severe intraventricular hemorrhage) was observed. CONCLUSION Zn supplementation for VLBW infants is found to be effective to decrease feeding intolerance, NEC, and LOS episodes in this vulnerable population. Current data support the supplementation of VLBW infants with higher than regular dose of Zn. KEY POINTS · Higher dose of Zn supplementation is shown to be a beneficial intervention in VLBW infants.. · Zn may decrease feeding intolerance, sepsis or NEC.. · Higher than regular dose of Zn seems to be safe..
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Affiliation(s)
- Suzan Sahin
- Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Izmir Demokrasi University, Izmir, Türkiye
| | - Fatma N Sari
- Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Türkiye
| | - Duygu Bidev
- Division of Neonatology, Department of Pediatrics, Koru Sincan Hospital, Ankara, Türkiye
| | - Ozlem Bozkurt
- Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Kocaeli University, Kocaeli, Türkiye
| | - Evrim A Dizdar
- Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Türkiye
| | - Serife S Oguz
- Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Türkiye
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Association of Zn and Cu Levels in Cord Blood and Maternal Milk with Pregnancy Outcomes among the Slovenian Population. Nutrients 2022; 14:nu14214667. [DOI: 10.3390/nu14214667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 10/16/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022] Open
Abstract
Trace elements, including zinc (Zn) and copper (Cu), are known to play important roles in human health. The present study aimed to assess the levels of Zn and Cu in cord blood and maternal milk and to analyze their association with maternal and infant characteristics and pregnancy outcomes in a Slovenian study population of mothers and their neonates recruited within the PHIME prospective cohort study. The study included 324 mothers, but the data on Zn and Cu levels in both cord blood and maternal milk was available for 243 mothers. Questionnaires were used to assess the socio-demographic and health status of the mothers, their lifestyle habits (including detailed nutritional habits), and their residential and occupational histories. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure Zn and Cu levels in cord blood and maternal milk. Low Zn levels in cord blood were associated with lower gestational age and birth weight and were correlated with an increased probability of the birth of small for gestational age (SGA) infants. Maternal smoking influenced the Cu levels in both cord blood and maternal milk. Cord blood Cu levels were higher and Cu levels in maternal milk were lower in smoking compared to non-smoking mothers. Most importantly, a decreased Zn/Cu ratio in cord blood was associated with lower gestational age and lower birth weight. This indicates the overall positive effects of Zn and negative effects of Cu on pregnancy outcomes.
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Sinha B, Dudeja N, Chowdhury R, Choudhary TS, Upadhyay RP, Rongsen-Chandola T, Mazumder S, Taneja S, Bhandari N. Enteral Zinc Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis. Pediatrics 2022; 150:188644. [PMID: 35921675 DOI: 10.1542/peds.2022-057092j] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/16/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97). There was no effect on acute respiratory infections, bacterial sepsis, and psychomotor development scores. The effect of zinc supplementation on mental development scores is inconclusive. There was no evidence of serious adverse events. Eight trials had some concerns or high risk of bias, small-sized studies, and high heterogeneity between trials led to moderate to very low certainty of evidence. CONCLUSIONS Zinc supplementation in preterm or LBW infants have benefits on growth and diarrhea prevention. Further research is needed to generate better quality evidence.
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Affiliation(s)
- Bireshwar Sinha
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.,DBT and Wellcome India Alliance Clinical and Public health Fellow, Hyderabad, India
| | - Nonita Dudeja
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India
| | - Ranadip Chowdhury
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.,DBT and Wellcome India Alliance Clinical and Public health Fellow, Hyderabad, India
| | - Tarun Shankar Choudhary
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.,Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Ravi Prakash Upadhyay
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.,DBT and Wellcome India Alliance Clinical and Public health Fellow, Hyderabad, India
| | | | - Sarmila Mazumder
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India
| | - Sunita Taneja
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India
| | - Nita Bhandari
- Centre for Health Research and Development, Society for Applied Studies, New Delhi, India
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Brion LP, Heyne R, Lair CS. Role of zinc in neonatal growth and brain growth: review and scoping review. Pediatr Res 2021; 89:1627-1640. [PMID: 33010794 DOI: 10.1038/s41390-020-01181-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 09/14/2020] [Accepted: 09/18/2020] [Indexed: 12/11/2022]
Abstract
This manuscript includes (1) a narrative review of Zinc as an essential nutrient for fetal and neonatal growth and brain growth and development and (2) a scoping review of studies assessing the effects of Zinc supplementation on survival, growth, brain growth, and neurodevelopment in neonates. Very preterm infants and small for gestational age infants are at risk for Zinc deficiency. Zinc deficiency can cause several complications including periorificial lesions, delayed wound healing, hair loss, diarrhea, immune deficiency, growth failure with stunting, and brain atrophy and dysfunction. Zinc is considered essential for oligodendrogenesis, neurogenesis, neuronal differentiation, white matter growth, and multiple biological and physiological roles in neurobiology. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks of gestation and extend until at least 44 weeks of postmenstrual age. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth, and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment. IMPACT: Zinc is essential for growth and brain growth and development. In the USA, very preterm small for gestational age infants are at risk for Zinc deficiency. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks' gestation and extend until at least 44 weeks of postmenstrual age. Several randomized trials of Zinc supplementation in neonates have shown improvement in growth when using high enough dose, for long duration in patients likely to or proven to have a Zinc deficiency. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment.
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Affiliation(s)
- Luc P Brion
- University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Roy Heyne
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Cheryl S Lair
- Parkland Health and Hospital System, Dallas, TX, USA
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Tee PS. Does enteral zinc supplementation improve growth and clinical outcome in preterm babies <37 weeks? J Paediatr Child Health 2020; 56:1971-1977. [PMID: 33351253 DOI: 10.1111/jpc.15215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 08/14/2020] [Accepted: 09/08/2020] [Indexed: 01/07/2023]
Abstract
AIM To review the literature of the benefits of enteral zinc supplementation in preterm population <37 weeks to improve growth and clinical outcome. METHODS PubMed database was searched for relevant articles. Studies not in English were excluded. RESULTS A total of 2678 results were identified. Duplicates were removed and titles were screened. References were reviewed to find other papers. Studies which include term infants were not examined although studies involving low birthweight infants with a defined percentage of preterm participants were examined. Thirty-four studies were subsequently reviewed, and nine studies were included as relevant to structured clinical question. CONCLUSION There are various levels of evidence suggesting benefits of enteral zinc supplementation in preterm babies. While the available trial findings are encouraging, there is currently limited evidence to address the effects of zinc supplementation in preterm infants in the setting of their typically long stay in Neonatal Intensive Care Unit. A larger multi-centre trial is required to establish optimal timing of initiation, dosage, duration and its effect on growth, development and acute morbidity and mortality.
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Affiliation(s)
- Pei Sen Tee
- Department of Neonatology, Cambridge University Hospitals NHS Foundation Trust, United Kingdom
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Lassi ZS, Kurji J, Oliveira CSD, Moin A, Bhutta ZA, Cochrane Neonatal Group. Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age. Cochrane Database Syst Rev 2020; 4:CD010205. [PMID: 32266964 PMCID: PMC7140593 DOI: 10.1002/14651858.cd010205.pub2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Zinc is a vital micronutrient for humans and is essential for protein synthesis, cell growth, and differentiation. Severe zinc deficiency can lead to slower physical, cognitive and sexual growth, cause skin disorders, decrease immunity, increase incidence of acute illnesses in infants and children and contribute to childhood stunting. By estimation, 17.3% of the world population is at risk of inadequate zinc intake. Such nutritional impairment increases the risk of diarrhoea and pneumonia by 20%, as well as leads to a global loss of more than 16 million disability-adjusted life years in children less than five years of age. Not only does zinc deficiency affect lives, it adds to the considerable financial burden on depleted resources in countries that are most affected. By preventing or curing this deficiency, we can improve childhood mortality, morbidity and growth. OBJECTIVES To assess the effectiveness of zinc supplementation for the promotion of growth, reduction in mortality, and the prevention of infections in infants less than six months of age. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 4), MEDLINE via PubMed (1966 to 18 May 2018), Embase (1980 to 18 May 2018), and CINAHL (1982 to 18 May 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. An updated search from 1 January 2018 to 29 January 2020 was run in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA All randomised controlled (individual and cluster randomised) and quasi-randomised trials of zinc supplementation in healthy, term infants, less than six months of age comparing infant mortality, incidence of diarrhoea or respiratory illnesses, growth and/or serum zinc levels were eligible. DATA COLLECTION AND ANALYSIS Two review authors screened search results (title and abstracts) and relevant full texts. Studies fulfilling prespecified inclusion criteria were included with any disagreements resolved by consensus. Extraction and analysis were then conducted. We used the GRADE approach to assess the quality of evidence as indicated by certainty in effect estimates. MAIN RESULTS Eight studies (with 85,629 infants) were included and five studies were meta-analysed, out of which four studies compared zinc with placebo, and one compared zinc plus riboflavin versus riboflavin. Certain growth outcomes after six months of intervention (Weight for Age Z-scores (WAZ) (standardised mean difference) (SMD) 0.16, 95% CI 0.03 to 0.29; three studies, n = 955; fixed-effect; heterogeneity Chi² P = 0.96); I² = 0%); change in WAZ (SMD 0.16, 95% CI 0.07 to 0.25; one study, n = 386; fixed-effect); (Weight-for-Length Z-score (WLZ) (SMD 0.15, 95% CI 0.02 to 0.28; three studies, n = 955; fixed-effect; heterogeneity: Chi² P = 0.81); I² = 0%); (change in WLZ (SMD 0.17, 95% CI 0.06 to 0.28; one study, n = 386; fixed-effect)) were positively affected by zinc supplementation compared to placebo. A single study reported no difference in the incidence of diarrhoea and lower respiratory tract infection with zinc supplementation. Zinc had no effect on mortality in children younger than 12 months. When zinc plus riboflavin was compared to riboflavin only, significant improvement was observed in the incidence of wasting at 24 months (risk ratio (RR) 0.59, 95% CI 0.37 to 0.96; one study, n = 296; fixed-effect), but significant worsening of incidence of stunting was present at 21 months (RR 1.53, 95% CI 1.09 to 2.16; one study, n = 298; fixed-effect). AUTHORS' CONCLUSIONS There was a significant positive impact of zinc supplementation on WAZ and WLZ after six months of intervention in infants compared to placebo. When a combined supplement of zinc and riboflavin was compared to riboflavin, there was a significant reduction in wasting at 24 months, but stunting at 21 months was negatively affected. Although included trials were of good-to-moderate quality, evidence that could be meta-analysed was based on a few studies which affected the overall quality of results. Regardless, there is a need for strong trials conducted in infants younger than six months before a strong recommendation can be made supporting zinc supplementation in this age group.
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Affiliation(s)
- Zohra S Lassi
- University of AdelaideRobinson Research InstituteAdelaideAustraliaAustralia
| | - Jaameeta Kurji
- University of OttawaSchool of Epidemiology and Public HealthOttawaCanada
| | | | - Anoosh Moin
- Aga Khan University HospitalDivision of Women and Child HealthStadium RoadPO Box 3500KarachiPakistan74800
| | - Zulfiqar A Bhutta
- The Hospital for Sick ChildrenCentre for Global Child HealthTorontoCanada
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Goudet SM, Bogin BA, Madise NJ, Griffiths PL, Cochrane Public Health Group. Nutritional interventions for preventing stunting in children (birth to 59 months) living in urban slums in low- and middle-income countries (LMIC). Cochrane Database Syst Rev 2019; 6:CD011695. [PMID: 31204795 PMCID: PMC6572871 DOI: 10.1002/14651858.cd011695.pub2] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Nutritional interventions to prevent stunting of infants and young children are most often applied in rural areas in low- and middle-income countries (LMIC). Few interventions are focused on urban slums. The literature needs a systematic assessment, as infants and children living in slums are at high risk of stunting. Urban slums are complex environments in terms of biological, social, and political variables and the outcomes of nutritional interventions need to be assessed in relation to these variables. For the purposes of this review, we followed the UN-Habitat 2004 definitions for low-income informal settlements or slums as lacking one or more indicators of basic services or infrastructure. OBJECTIVES To assess the impact of nutritional interventions to reduce stunting in infants and children under five years old in urban slums from LMIC and the effect of nutritional interventions on other nutritional (wasting and underweight) and non-nutritional outcomes (socioeconomic, health and developmental) in addition to stunting. SEARCH METHODS The review used a sensitive search strategy of electronic databases, bibliographies of articles, conference proceedings, websites, grey literature, and contact with experts and authors published from 1990. We searched 32 databases, in English and non-English languages (MEDLINE, CENTRAL, Web of Science, Ovid MEDLINE, etc). We performed the initial literature search from November 2015 to January 2016, and conducted top up searches in March 2017 and in August 2018. SELECTION CRITERIA Research designs included randomised (including cluster-randomised) trials, quasi-randomised trials, non-randomised controlled trials, controlled before-and-after studies, pre- and postintervention, interrupted time series (ITS), and historically controlled studies among infants and children from LMIC, from birth to 59 months, living in urban slums. The interventions included were nutrition-specific or maternal education. The primary outcomes were length or height expressed in cm or length-for-age (LFA)/height-for-age (HFA) z-scores, and birth weight in grams or presence/absence of low birth weight (LBW). DATA COLLECTION AND ANALYSIS We screened and then retrieved titles and abstracts as full text if potentially eligible for inclusion. Working independently, one review author screened all titles and abstracts and extracted data on the selected population, intervention, comparison, and outcome parameters and two other authors assessed half each. We calculated mean selection difference (MD) and 95% confidence intervals (CI). We performed intervention-level meta-analyses to estimate pooled measures of effect, or narrative synthesis when meta-analyses were not possible. We used P less than 0.05 to assess statistical significance and intervention outcomes were also considered for their biological/health importance. Where effect sizes were small and statistically insignificant, we concluded there was 'unclear effect'. MAIN RESULTS The systematic review included 15 studies, of which 14 were randomised controlled trials (RCTs). The interventions took place in recognised slums or poor urban or periurban areas. The study locations were mainly Bangladesh, India, and Peru. The participants included 9261 infants and children and 3664 pregnant women. There were no dietary intervention studies. All the studies identified were nutrient supplementation and educational interventions. The interventions included zinc supplementation in pregnant women (three studies), micronutrient or macronutrient supplementation in children (eight studies), nutrition education for pregnant women (two studies), and nutrition systems strengthening targeting children (two studies) intervention. Six interventions were adapted to the urban context and seven targeted household, community, or 'service delivery' via systems strengthening. The primary review outcomes were available from seven studies for LFA/HFA, four for LBW, and nine for length.The studies had overall high risk of bias for 11 studies and only four RCTs had moderate risk of bias. Overall, the evidence was complex to report, with a wide range of outcome measures reported. Consequently, only eight study findings were reported in meta-analyses and seven in a narrative form. The certainty of evidence was very low to moderate overall. None of the studies reported differential impacts of interventions relevant to equity issues.Zinc supplementation of pregnant women on LBW or length (versus supplementation without zinc or placebo) (three RCTs)There was no evidence of an effect on LBW (MD -36.13 g, 95% CI -83.61 to 11.35), with moderate-certainty evidence, or no evidence of an effect or unclear effect on length with low- to moderate-certainty evidence.Micronutrient or macronutrient supplementation in children (versus no intervention or placebo) (eight RCTs)There was no evidence of an effect or unclear effect of nutrient supplementation of children on HFA for studies in the meta-analysis with low-certainty evidence (MD -0.02, 95% CI -0.06 to 0.02), and inconclusive effect on length for studies reported in a narrative form with very low- to moderate-certainty evidence.Nutrition education for pregnant women (versus standard care or no intervention) (two RCTs)There was a positive impact on LBW of education interventions in pregnant women, with low-certainty evidence (MD 478.44g, 95% CI 423.55 to 533.32).Nutrition systems strengthening interventions targeting children (compared with no intervention, standard care) (one RCT and one controlled before-and-after study)There were inconclusive results on HFA, with very low- to low-certainty evidence, and a positive influence on length at 18 months, with low-certainty evidence. AUTHORS' CONCLUSIONS All the nutritional interventions reviewed had the potential to decrease stunting, based on evidence from outside of slum contexts; however, there was no evidence of an effect of the interventions included in this review (very low- to moderate-certainty evidence). Challenges linked to urban slum programming (high mobility, lack of social services, and high loss of follow-up) should be taken into account when nutrition-specific interventions are proposed to address LBW and stunting in such environments. More evidence is needed of the effects of multi-sectorial interventions, combining nutrition-specific and sensitive methods and programmes, as well as the effects of 'up-stream' practices and policies of governmental, non-governmental organisations, and the business sector on nutrition-related outcomes such as stunting.
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Affiliation(s)
- Sophie M Goudet
- Loughborough UniversityCentre for Global Health and Human Development, School of Sport, Exercise and Health SciencesLoughboroughLeicestershireUKLE11 3TU
| | - Barry A Bogin
- Loughborough UniversityCentre for Global Health and Human Development, School of Sport, Exercise and Health SciencesLoughboroughLeicestershireUKLE11 3TU
| | | | - Paula L Griffiths
- Loughborough UniversityCentre for Global Health and Human Development, School of Sport, Exercise and Health SciencesLoughboroughLeicestershireUKLE11 3TU
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Gera T, Shah D, Sachdev HS. Zinc Supplementation for Promoting Growth in Children Under 5 years of age in Low- and Middle-income Countries: A Systematic Review. Indian Pediatr 2019. [DOI: 10.1007/s13312-019-1537-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Ariff S, Krebs NF, Westcott JE, Hambidge M, Miller LV, Rizvi A, Soofi SB, Bhutta ZA. Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants. J Pediatr Gastroenterol Nutr 2018; 66:496-500. [PMID: 29470320 PMCID: PMC6343844 DOI: 10.1097/mpg.0000000000001778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined. METHODS In a community-based, observational, longitudinal study in a peri-urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP. RESULTS No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ± 3.5 and 10.1 ± 4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017). CONCLUSIONS These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.
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Affiliation(s)
| | - Nancy F. Krebs
- Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, CO
| | - Jamie E. Westcott
- Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, CO
| | - Michael Hambidge
- Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, CO
| | - Leland V. Miller
- Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Anschutz Medical Center, Aurora, CO
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Lazarus RP, John J, Shanmugasundaram E, Rajan AK, Thiagarajan S, Giri S, Babji S, Sarkar R, Kaliappan PS, Venugopal S, Praharaj I, Raman U, Paranjpe M, Grassly NC, Parker EPK, Parashar UD, Tate JE, Fleming JA, Steele AD, Muliyil J, Abraham AM, Kang G. The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants. Vaccine 2018; 36:273-279. [PMID: 28874323 PMCID: PMC12001858 DOI: 10.1016/j.vaccine.2017.07.116] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 07/20/2017] [Accepted: 07/28/2017] [Indexed: 01/25/2023]
Abstract
BACKGROUND Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION The trial was registered in India (CTRI/2012/05/002677).
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Affiliation(s)
- Robin P Lazarus
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Jacob John
- Department of Community Health, Christian Medical College, Vellore, India
| | - E Shanmugasundaram
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Anand K Rajan
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - S Thiagarajan
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Sidhartha Giri
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Sudhir Babji
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Rajiv Sarkar
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | | | - Srinivasan Venugopal
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Ira Praharaj
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Uma Raman
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Meghana Paranjpe
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Nicholas C Grassly
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - Edward P K Parker
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | | | | | | | | | - Jayaprakash Muliyil
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Asha M Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Gagandeep Kang
- Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
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Nunan M, Horoto W, Manea T, Duncan G, Duke T. Scaling up zinc treatment for childhood diarrhoea in the developing country setting: a before- and after-intervention study. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2017. [DOI: 10.1002/jppr.1197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Michael Nunan
- Centre for International Child Health; University of Melbourne; Parkville Australia
| | - William Horoto
- National Pharmacy Services Division; Ministry of Health and Medical Services; Honiara Solomon Islands
- Solomon Islands Ministry of Health and Medical Services; Honiara Solomon Islands
| | - Timmy Manea
- National Pharmacy Services Division; Ministry of Health and Medical Services; Honiara Solomon Islands
- Solomon Islands Ministry of Health and Medical Services; Honiara Solomon Islands
| | - Greg Duncan
- Faculty of Medicine, Nursing and Health Science; Monash University; Melbourne Australia
| | - Trevor Duke
- Centre for International Child Health; University of Melbourne; Parkville Australia
- School of Medicine; University of Papua New Guinea; Port Moresby PNG
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Abstract
BACKGROUND In developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using either a fixed-effect or random-effects model) and assessed heterogeneity.We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS Thirty-three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency. Acute diarrhoeaThere is currently not enough evidence from well-conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence).In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD -11.46 hours, 95% CI -19.72 to -3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD -26.39 hours, 95% CI -36.54 to -16.23; 419 children, 5 trials, high certainty evidence).Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, 2 trials, moderate certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, moderate certainty evidence).None of the included trials reported serious adverse events. However, zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence). Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, 5 trials, moderate certainty evidence). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well-nourished children, and in settings where children are at low risk of zinc deficiency.
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Affiliation(s)
- Marzia Lazzerini
- Institute for Maternal and Child Health IRCCS Burlo GarofoloWHO Collaborating Centre for Maternal and Child HealthVia dell'Istria 65/1, 34137TriesteItaly
| | - Humphrey Wanzira
- Institute for Maternal and Child Health IRCCS Burlo GarofoloWHO Collaborating Centre for Maternal and Child HealthVia dell'Istria 65/1, 34137TriesteItaly
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13
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Nissensohn M, Sánchez-Villegas A, Fuentes Lugo D, Henríquez Sánchez P, Doreste Alonso J, Peña Quintana L, Ruano C, Lowe NL, Hall Moran V, Skinner AL, Warthon-Medina M, Serra-Majem L. Effect of Zinc Intake on Growth in Infants: A Meta-analysis. Crit Rev Food Sci Nutr 2016; 56:350-63. [PMID: 25365524 DOI: 10.1080/10408398.2013.802661] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
A systematic review and meta-analysis of available randomized controlled trials (RCTs) was conducted to evaluate the effect of zinc (Zn) intake on growth in infants. Out of 5500 studies identified through electronic searches and reference lists, 19 RCTs were selected after applying the exclusion/inclusion criteria. The influence of Zn intake on growth was considered in the overall meta-analysis. Other variables were also taken into account as possible effect modifiers: doses of Zn intake, intervention duration, nutritional status, and risk of bias. From each select growth study, final measures of weight, length, mid upper arm circumference (MUAC), head circumference, weight for age z-score (WAZ), length for age z-score (LAZ), and weight for length z-score (WLZ) were assessed. Pooled β and 95% confidence interval (CI) were calculated. Additionally, we carried out a sensitivity analysis. Zn intake was not associated with weight, length, MUAC, head circumference, and LAZ in the pooled analyses. However, Zn intake had a positive and statistically effect on WAZ (β = 0.06; 95%CI 0.02 to 0.10) and WLZ (β = 0.05; 95%CI 0.01 to 0.08). The dose-response relationship between Zn intake and these parameters indicated that a doubling of Zn intake increased WAZ and WLZ by approximately 4%. Substantial heterogeneity was present only in length analyses (I(2) = 45%; p = 0.03). Zn intake was positively associated with length values at short time (four to 20 weeks) (β = 0.01; CI 95% 0 to 0.02) and at medium doses of Zn (4.1 to 8 mg/day) (β = 0.003; CI 95% 0 to 0.01). Nevertheless, the effect magnitude was small. Our results indicate that Zn intake increases growth parameters of infants. Nonetheless, interpretation of these results should be carefully considered.
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Affiliation(s)
- M Nissensohn
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
| | - A Sánchez-Villegas
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
| | - D Fuentes Lugo
- c Faculty of Health Sciences, Universidad Autónoma del Carmen (Unacar), Ciudad del Carmen . México
| | - P Henríquez Sánchez
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
| | - J Doreste Alonso
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
| | - L Peña Quintana
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain.,d Unit of Gastroenterology, Hepatology and Pediatric Nutrition. Complejo Hospitalario Universitario Insular Materno-Infantil de Las Palmas, Las Palmas de Gran Canaria , Spain
| | - C Ruano
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
| | - N L Lowe
- e International Institute of Nutritional Sciences and Applied Food Safety Studies, University of Central Lancashire , Preston , UK
| | - V Hall Moran
- f Maternal & Infant Nutrition & Nurture Unit, University of Central Lancashire , Preston , UK
| | - A L Skinner
- e International Institute of Nutritional Sciences and Applied Food Safety Studies, University of Central Lancashire , Preston , UK
| | - M Warthon-Medina
- e International Institute of Nutritional Sciences and Applied Food Safety Studies, University of Central Lancashire , Preston , UK
| | - L Serra-Majem
- a Research Institute of Biomedical and Health Sciences, Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Facultad de Ciencias de la Salud, Las Palmas de Gran Canaria , Spain.,b Ciber Obn. Physiopathology of Obesity and Nutrition, Institute of Health "Carlos III," Madrid , Spain
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14
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Lassi ZS, Moin A, Bhutta ZA, Cochrane Acute Respiratory Infections Group. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2016; 12:CD005978. [PMID: 27915460 PMCID: PMC6463931 DOI: 10.1002/14651858.cd005978.pub3] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily zinc supplements have been reported to prevent acute lower respiratory tract infection (LRTI) and reduce child mortality. This is an update of a review first published in 2010. OBJECTIVES To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months. SEARCH METHODS We searched CENTRAL (Issue 21 October 2016), MEDLINE (1966 to October 2016), Embase (1974 to October 2016), LILACS (1982 to October 2016), CINAHL (1981 to October 2016), Web of Science (1985 to October 2016) and IMSEAR (1980 to October 2016). SELECTION CRITERIA Randomised controlled trials (RCTs) evaluating zinc supplementation for the prevention of pneumonia in children aged from 2 months to 59 months. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. MAIN RESULTS We did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants.Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932). AUTHORS' CONCLUSIONS Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia.
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Affiliation(s)
- Zohra S Lassi
- The University of AdelaideThe Robinson Research InstituteAdelaideSouth AustraliaAustralia5005
| | - Anoosh Moin
- Aga Khan University HospitalDivision of Women and Child HealthStadium RoadPO Box 3500KarachiPakistan74800
| | - Zulfiqar A Bhutta
- Hospital for Sick ChildrenCenter for Global Child HealthTorontoONCanadaM5G A04
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The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis. Nutrients 2016; 8:nu8120773. [PMID: 27916873 PMCID: PMC5188428 DOI: 10.3390/nu8120773] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 11/23/2016] [Accepted: 11/24/2016] [Indexed: 12/26/2022] Open
Abstract
Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6–23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L (p < 0.001) and mean serum ferritin concentration by 17.6 µg/L (p < 0.001) and reduced the risk for anemia by 41% (p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L (p < 0.001) and reduced the risk of zinc deficiency by 47% (p < 0.001). Further, we observed positive effects on child weight for age z-score (WAZ) (p < 0.05), weight for height z-score (WHZ) (p < 0.05), but not on height for age z-score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6–23 months of age has a positive effect on child iron and zinc status.
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16
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Abstract
BACKGROUND Low birth weight (birth weight<2500 g) is one of the major determinants of neonatal morbidity as well as mortality and these are known to be significantly higher in these infants. OBJECTIVE To study the morbidity pattern of low-birth-weight (LBW) infants in an urban slum in Kolkata, India. MATERIALS AND METHODS A follow-up community-based study was undertaken in 2004-2005 in an urban slum of Chetla (Kolkata, West Bengal, India), among 126 singleton live-born babies, who were followed up for 9 months at 15±5 days interval by home visits. RESULTS Incidence of LBW was 28.6%. Morbidity episodes and hospitalization rate were more in LBW than in normal-birth-weight infants. Overall, gastrointestinal infection and acute respiratory infection were predominant in both LBW and normal-birth-weight babies. CONCLUSION AND RECOMMENDATIONS Although morbidity episodes as well as hospitalization rate were lower compared with other studied slums of India, there is still room for further improvement of health status of these babies. Adequate care, exclusive breast-feeding, and proper nutrition of the LBW infants must be ensured to have healthy lifestyle free from morbidity.
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Terrin G, Berni Canani R, Di Chiara M, Pietravalle A, Aleandri V, Conte F, De Curtis M. Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate. Nutrients 2015; 7:10427-46. [PMID: 26690476 PMCID: PMC4690094 DOI: 10.3390/nu7125542] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2015] [Revised: 11/23/2015] [Accepted: 11/26/2015] [Indexed: 11/26/2022] Open
Abstract
Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated.
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Affiliation(s)
- Gianluca Terrin
- Department of Gynecology-Obstetrics, University of Rome La Sapienza, Rome 00186, Italy.
| | - Roberto Berni Canani
- Department of Translational Medicine, University of Naples Federico II, Napoli 80138, Italy.
| | - Maria Di Chiara
- Department of Gynecology-Obstetrics, University of Rome La Sapienza, Rome 00186, Italy.
| | - Andrea Pietravalle
- Department of Gynecology-Obstetrics, University of Rome La Sapienza, Rome 00186, Italy.
| | - Vincenzo Aleandri
- Department of Gynecology-Obstetrics, University of Rome La Sapienza, Rome 00186, Italy.
- Research Center on Evaluation of Quality in Medicine-CEQUAM, University of Rome La Sapienza, Rome 00186, Italy.
| | - Francesca Conte
- Department of Pediatrics, University of Rome La Sapienza, Rome 00186, Italy.
| | - Mario De Curtis
- Department of Pediatrics, University of Rome La Sapienza, Rome 00186, Italy.
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18
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Tran CD, Gopalsamy GL, Mortimer EK, Young GP. The potential for zinc stable isotope techniques and modelling to determine optimal zinc supplementation. Nutrients 2015; 7:4271-95. [PMID: 26035248 PMCID: PMC4488783 DOI: 10.3390/nu7064271] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 05/18/2015] [Indexed: 01/17/2023] Open
Abstract
It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease.
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Affiliation(s)
- Cuong D Tran
- CSIRO Food and Nutrition Flagship, Gate 13, Kintore Ave, Adelaide SA 5000, Australia.
- School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide SA 5005, Australia.
| | - Geetha L Gopalsamy
- CSIRO Food and Nutrition Flagship, Gate 13, Kintore Ave, Adelaide SA 5000, Australia.
- Flinders University of South Australia, Bedford Park, GPO Box 2100, Adelaide SA 5001, Australia.
| | - Elissa K Mortimer
- Flinders University of South Australia, Bedford Park, GPO Box 2100, Adelaide SA 5001, Australia.
| | - Graeme P Young
- Flinders University of South Australia, Bedford Park, GPO Box 2100, Adelaide SA 5001, Australia.
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Paul A, Gladstone BP, Mukhopadhya I, Kang G. Rotavirus infections in a community based cohort in Vellore, India. Vaccine 2015; 32 Suppl 1:A49-54. [PMID: 25091680 DOI: 10.1016/j.vaccine.2014.03.039] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The burden of infection in communities determines the spread of rotavirus infection and disease in susceptible populations. This study reports rotavirus infection and disease in a community based birth cohort in Vellore. METHODS Bimonthly surveillance and diarrheal stool were collected from 452 children enrolled at birth, of whom 373 completed three years of follow up. Samples were screened for rotavirus by an ELISA and genotyped by reverse transcription polymerase chain reaction for VP7 and VP4 genes. Rotavirus incidence rates were calculated using Poisson regression equations. Risk factors associated with symptomatic and asymptomatic rotavirus infections were compared using multiple logistic regression. RESULTS A total of 1149 episodes of rotavirus infections occurred in 94.4% children in the cohort. Incidence of rotavirus infection was 1.04 (0.97-1.1) per child-year with 0.75 asymptomatic and 0.29 symptomatic infections per child-year. About 18% of the children were infected in the first month, mainly with the G10P[11] strain. Rotavirus infections were more prevalent during October-March, but seasonality was not as marked in rotavirus disease. Rotavirus was associated with 15.1% of mild diarrhea, 38.9% of moderate/severe diarrhea and 66.7% of very severe diarrhea. Four common G types - G1 (26.8%), G2 (16%), G10 (11.2%) and G9 (9.6%) were seen, with high rates of mixed infections and untypable samples. Male gender, presence of siblings and low maternal education were associated with rotavirus disease. CONCLUSION This study demonstrates that rotavirus is the most common cause of gastroenteritis in the community, and indicates that since rotavirus caused the greatest proportion of moderate and severe disease, targeted interventions such as vaccines are needed for rotavirus, in addition to health education, sanitation and appropriate treatment to decrease diarrheal disease in communities.
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Affiliation(s)
- Anu Paul
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Beryl P Gladstone
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Indrani Mukhopadhya
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Gagandeep Kang
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
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Krebs NF, Miller LV, Hambidge KM. Zinc deficiency in infants and children: a review of its complex and synergistic interactions. Paediatr Int Child Health 2014; 34:279-88. [PMID: 25203844 DOI: 10.1179/2046905514y.0000000151] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Zinc deficiency is estimated to contribute to over half a million deaths per year in infants and children under 5 years of age. This paper reviews the features of mild-to-moderate zinc deficiency, which include growth faltering, deficits in immune function and altered integrity and function of the gastro-intestinal tract. Sub-clinical features include oxidative stress and a pro-inflammatory state. The homeostatic response to low dietary zinc intake by increasing absorption is limited, especially if the source of zinc is of poor bioavailability, and conservation of endogenous intestinal losses is a critical component of adaptation. Owing to low zinc intakes, older breastfed infants, especially those of low birthweight, are predictably at risk of zinc deficiency if complementary food choices are unfortified and/or low in zinc. Host factors such as young age, poor intra-uterine zinc accretion owing to poor maternal status and/or prematurity, and gastro-intestinal dysfunction also potently predispose to zinc deficiency. Environmental enteropathy, which is prevalent in low-resource settings, may substantially impair zinc absorption and/or increase endogenous losses, and thus lead to relatively high zinc requirements. Emerging evidence highlights common features between chronic inflammation and zinc deficiency, and each may exacerbate the other. More investigations of zinc homeostasis in populations in low-resource settings are needed to better quantify absorption capacity and losses. Effective preventive strategies must address potentially higher zinc requirements as well as the underlying context that perpetuates a vicious cycle of zinc deficiency and multiple adverse outcomes.
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Gulani A, Sachdev HS, Cochrane Acute Respiratory Infections Group. Zinc supplements for preventing otitis media. Cochrane Database Syst Rev 2014; 2014:CD006639. [PMID: 24974096 PMCID: PMC9392835 DOI: 10.1002/14651858.cd006639.pub4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Otitis media is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent otitis media. OBJECTIVES To evaluate whether zinc supplements prevent otitis media in adults and children of different ages. SEARCH METHODS We searched CENTRAL (2014, Issue 1), MEDLINE (1950 to February week 4, 2014) and EMBASE (1974 to March 2014). SELECTION CRITERIA Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS No new trials were identified for inclusion in this update. We identified 12 trials for inclusion, 10 of which contributed outcomes data. There were a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc-supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow-up (3191 participants); another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of otitis media (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias. AUTHORS' CONCLUSIONS Evidence on whether zinc supplementation can reduce the incidence of otitis media in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition), but this is based on one small trial and should therefore be treated with caution.
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Affiliation(s)
- Anjana Gulani
- Max Multispeciality CentreDepartment of PediatricsN‐110, Panchsheel ParkNew DelhiIndia110017
- Max Superspeciality HospitalDepartment of Pediatrics and NeonatologySaketNew DelhiIndia
| | - Harshpal S Sachdev
- Sitaram Bhartia Institute of Science and ResearchDepartment of Pediatrics and Clinical EpidemiologyB‐16 Qutab Institutional AreaNew DelhiIndia110016
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Enteral zinc supplementation and growth in extremely-low-birth-weight infants with chronic lung disease. J Pediatr Gastroenterol Nutr 2014; 58:183-7. [PMID: 24121149 PMCID: PMC4125018 DOI: 10.1097/mpg.0000000000000145] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Zinc deficiency causes growth deficits. Extremely-low-birth-weight (ELBW) infants with chronic lung disease (CLD), also known as bronchopulmonary dysplasia, experience growth failure and are at risk for zinc deficiency. We hypothesized that enteral zinc supplementation would increase weight gain and linear growth. METHODS A cohort of infants was examined retrospectively at a single center between January 2008 and December 2011. CLD was defined as the need for oxygen at 36 weeks postmenstrual age. Zinc supplementation was started in infants who had poor weight gain. Infants' weight gain and linear growth were compared before and after zinc supplementation using the paired t test. RESULTS A total of 52 ELBW infants with CLD met entry criteria. Mean birth weight was 682 ± 183 g, and gestational age was 25.3 ± 2 weeks. Zinc supplementation started at postmenstrual age 33 ± 2 weeks. Most infants received fortified human milk. Weight gain increased from 10.9 before supplementation to 19.9 g · kg(-1) · day(-1) after supplementation (P < 0.0001). Linear growth increased from 0.7 to 1.1 cm/week (P = 0.001). CONCLUSIONS Zinc supplementation improved growth in ELBW infants with CLD receiving human milk. Further investigation is warranted to reevaluate zinc requirements, markers, and balance.
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Terrin G, Berni Canani R, Passariello A, Messina F, Conti MG, Caoci S, Smaldore A, Bertino E, De Curtis M. Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country. Am J Clin Nutr 2013; 98:1468-74. [PMID: 24025633 DOI: 10.3945/ajcn.112.054478] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. OBJECTIVE The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. DESIGN This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. RESULTS We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478). CONCLUSION Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.
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Affiliation(s)
- Gianluca Terrin
- Department of Gynecology-Obstetrics and Perinatal Medicine, University "La Sapienza," Rome, Italy (GT); the Department of Translational Medicine-Pediatric Section and European Laboratory for the Investigation of Food Induced Diseases, University of Naples "Federico II," Naples, Italy (RBC and AS); the Department of Intensive Care, Hospital "Dei Colli," Naples, Italy (AP); the Department of Perinatal Care, Evangelic Hospital "V Betania," Naples, Italy (FM); the Department of Pediatrics, University "La Sapienza," Rome, Italy (MGC, SC, and MDC); and the Department of Pediatrics, University of Turin, Turin, Italy (EB)
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Qadir MI, Arshad A, Ahmad B. Zinc: Role in the management of diarrhea and cholera. World J Clin Cases 2013; 1:140-142. [PMID: 24303485 PMCID: PMC3845954 DOI: 10.12998/wjcc.v1.i4.140] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Revised: 05/30/2013] [Accepted: 06/08/2013] [Indexed: 02/05/2023] Open
Abstract
Diarrhea and cholera are major health problems. Vibrio cholera, the causative agent of cholera, infects the small intestine, resulting in vomiting, massive watery diarrhea and dehydration. Reduced water and electrolyte absorption is also due to zinc deficiency. Zinc has an important role in recovery from the disease. The combination of zinc with cholera vaccine and oral rehydration solutions has a positive impact on cholera and diarrhea. It has led to a decrease in the mortality and morbidity associated with diarrhea.
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Malik A, Taneja DK, Devasenapathy N, Rajeshwari K. Short-course prophylactic zinc supplementation for diarrhea morbidity in infants of 6 to 11 months. Pediatrics 2013; 132:e46-52. [PMID: 23733798 DOI: 10.1542/peds.2012-2980] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Zinc supplementation during diarrhea substantially reduces the incidence and severity of diarrhea. However, the effect of short-course zinc prophylaxis has been observed only in children >12 months of age. Because the incidence of diarrhea is comparatively high in children aged 6 to 11 months, we assessed the prophylactic effect of zinc on incidence and duration of diarrhea in this age group. METHODS In this randomized, double-blind, placebo-controlled trial, we enrolled infants aged 6 to 11 months from an urban resettlement colony in Delhi, India, between January 1, 2011, and January 15, 2012. We randomly assigned 272 infants to receive either 20 mg of zinc or a placebo suspension orally every day for 2 weeks. The primary outcome was the incidence of diarrhea per child-year. All analyses were done by intention-to-treat. RESULTS A total of 134 infants in the zinc and 124 in the placebo groups were assessed for the incidence of diarrhea. There was a 39% reduction (crude incident rate ratio [IRR] 0.61, 95% confidence interval [CI] 0.53-0.71) in episodes of diarrhea, 39% (adjusted IRR 0.61, 95% CI 0.54-0.69) in the total number of days that a child suffered from diarrhea, and reduction of 36% in duration per episode of diarrhea (IRR 0.64, 95% CI 0.56-0.74) during the 5 months of follow-up. CONCLUSIONS Short-course prophylactic zinc supplementation for 2 weeks may reduce diarrhea morbidity in infants of 6 to 11 months for up to 5 months, in populations with high prevalence of wasting and stunting.
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Affiliation(s)
- Akash Malik
- Department of Community Medicine, Maulana Azad Medical College, New Delhi, India.
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Abstract
BACKGROUND In developing countries, diarrhoea causes around two million child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization and UNICEF. OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials comparing oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity.The quality of evidence has been assessed using the GRADE methods MAIN RESULTS Twenty-four trials, enrolling 9128 children, met our inclusion criteria. The majority of the data is from Asia, from countries at high risk of zinc deficiency, and may not be applicable elsewhere. Acute diarrhoea. There is currently not enough evidence from well conducted randomized controlled trials to be able to say whether zinc supplementation during acute diarrhoea reduces death or hospitalization (very low quality evidence).In children aged greater than six months with acute diarrhoea, zinc supplementation may shorten the duration of diarrhoea by around 10 hours (MD -10.44 hours, 95% CI -21.13 to 0.25; 2175 children, six trials, low quality evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, six trials, moderate quality evidence). In children with signs of moderate malnutrition the effect appears greater, reducing the duration of diarrhoea by around 27 hours (MD -26.98 hours, 95% CI -14.62 to -39.34; 336 children, three trials, high quality evidence).Conversely, In children aged less than six months, the available evidence suggests zinc supplementation may have no effect on mean diarrhoea duration (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, two trials, low quality evidence), and may even increase the proportion of children whose diarrhoea persists until day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, one trial, moderate quality evidence).No trials reported serious adverse events, but zinc supplementation during acute diarrhoea causes vomiting in both age groups (RR 1.59, 95% 1.27 to 1.99; 5189 children, 10 trials, high quality evidence). Persistent diarrhoea. In children with persistent diarrhoea, zinc supplementation probably shortens the duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, five trials, moderate quality evidence). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of moderate malnutrition is high, zinc may be of benefit in children aged six months or more.The current evidence does not support the use of zinc supplementation in children below six months of age.
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Affiliation(s)
- Marzia Lazzerini
- Unit for Health Services Research and International Health,WHO Collaborating Centre forMaternal and ChildHealth, Institute forMaternal and Child Health, Trieste, Italy.
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Abstract
BACKGROUND In developing countries, diarrhoea causes around two million child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization and UNICEF. OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials comparing oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity.The quality of evidence has been assessed using the GRADE methods MAIN RESULTS Twenty-four trials, enrolling 9128 children, met our inclusion criteria. The majority of the data is from Asia, from countries at high risk of zinc deficiency, and may not be applicable elsewhere.Acute diarrhoeaThere is currently not enough evidence from well conducted randomized controlled trials to be able to say whether zinc supplementation during acute diarrhoea reduces death or hospitalization (very low quality evidence).In children aged greater than six months with acute diarrhoea, zinc supplementation may shorten the duration of diarrhoea by around 10 hours (MD -10.44 hours, 95% CI -21.13 to 0.25; 2091 children, five trials, low quality evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, six trials, moderate quality evidence). In children with signs of moderate malnutrition the effect appears greater, reducing the duration of diarrhoea by around 27 hours (MD -26.98 hours, 95% CI -14.62 to -39.34; 336 children, three trials, high quality evidence).Conversely, In children aged less than six months, the available evidence suggests zinc supplementation may have no effect on mean diarrhoea duration (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, two trials, low quality evidence), and may even increase the proportion of children whose diarrhoea persists until day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, one trial, moderate quality evidence).No trials reported serious adverse events, but zinc supplementation during acute diarrhoea causes vomiting in both age groups (RR 1.59, 95% 1.27 to 1.99; 5189 children, 10 trials, high quality evidence).Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, five trials, moderate quality evidence). AUTHORS' CONCLUSIONS In areas where the prevalence of zinc deficiency or the prevalence of moderate malnutrition is high, zinc may be of benefit in children aged six months or more.The current evidence does not support the use of zinc supplementation in children below six months of age.
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Affiliation(s)
- Marzia Lazzerini
- Unit for Health Services Research and International Health,WHO Collaborating Centre forMaternal and ChildHealth, Institute forMaternal and Child Health, Trieste, Italy.
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Abstract
BACKGROUND Otitis media (OM) is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent OM. OBJECTIVES To evaluate whether zinc supplements prevent OM in adults and children of different ages. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 1) which includes the Cochrane Acute Respiratory Infections Groups' Specialised Register, MEDLINE (1950 to February week 1, 2012) and EMBASE (1974 to February 2012). SELECTION CRITERIA Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing OM. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS We identified 12 trials for inclusion, 10 of which contributed outcomes data. There was a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite OM during follow-up (3191 participants); another trial showed a significantly lower incidence rate of OM in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of OM (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias. AUTHORS' CONCLUSIONS Evidence on whether zinc supplementation can reduce the incidence of OM in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition) but this is based on one small trial and should therefore be treated with caution.
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Affiliation(s)
- Anjana Gulani
- Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, India.
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Abstract
This was a randomized blinded placebo controlled trial undertaken to study the role of zinc supplementation on growth, primarily the linear growth velocity in very low birth weight (VLBW) infants at 3 months corrected age (CA). Out of 134 neonates with birth weight <1500 g, 101 babies were eligible. Due to lack of consent 10 were excluded. The remaining 91 neonates who were comparable for sex, gestational age, birth weight, APGAR and age at enrollment were randomized to receive either 1 ml of zinc sulfate (10 mg elemental zinc) (n = 46) or 1 ml placebo (n = 45) from enrollment to 60 days. The infants in the zinc group had significantly higher linear growth velocity (0.98 ± 0.12 cm week(-1)) compared to a placebo group (0.67 ± 0.15 cm week(-1)) (p < 0.001) at 3 months CA. We concluded that zinc supplementation at 10 mg day(-1) for 60 days in VLBW infants improves their linear growth during infancy.
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Affiliation(s)
- T V Ram Kumar
- Neonatal Division, Department of Pediatrics, Maulana Azad Medical College, New Delhi 110002, India.
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Aminisani N, Barak M, Shamshirgaran SM. Effect of zinc supplementation on growth of low birth weight infants aged 1-6 mo in Ardabil, Iran. Indian J Pediatr 2011; 78:1239-43. [PMID: 21858548 DOI: 10.1007/s12098-011-0541-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 07/14/2011] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To assess the effect of zinc supplementation on growth of low birth weight (LBW) infants aged 1-6 mo. METHODS LBW infants were enrolled at birth and randomly assigned to receive 5 mg elemental Zn per day (n = 45) or placebo (n = 45) until 6 mo of age. They were followed monthly for information on compliance; anthropometric measurements were performed monthly. RESULTS After randomization, 5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age, significantly greater weight gains were observed in the zinc than in the placebo group (4995 ± 74 g in zinc group vs. 3896 ± 865 g in placebo group, p=0.036). Length gain during the study period improved in zinc group (16.9 ± 8.2 cm vs. 15.1 ± 4.1 cm, p=0.039); after zinc supplementation head circumference were increased (8.7 ± 1.4 cm vs. 7.4 ± 1.5 cm p < 0.001). In male infants, total weight gain and height and head circumference gain were higher in the zinc than in the placebo group. However, only head circumference change was statistically significant. A similar trend was observed among female infants, but these differences were not statistically significant. There was no significant relation between breast-feeding status and the main outcome variables. CONCLUSIONS Infants in the present study showed improvements in growth rate, but more studies are required in this field to confirm this fact.
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Affiliation(s)
- Nayyereh Aminisani
- Biostatistics and Epidemiology, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
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Gulani A, Bhatnagar S, Sachdev HPS. Neonatal zinc supplementation for prevention of mortality and morbidity in breastfed low birth weight infants: systematic review of randomized controlled trials. Indian Pediatr 2011; 48:111-7. [PMID: 21378420 DOI: 10.1007/s13312-011-0043-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To evaluate whether zinc supplements prevent mortality and morbidity in breastfed low birth weight infants. METHODS All randomized or qausi-randomized trials with individual or cluster allocation and using concurrent controls were included. Study population included LBW infants irrespective of gestational status who were exclusively or predominantly breastfed at the initiation of intervention. Intervention comprised zinc salts given as tablets or syrups orally to provide at least 1 RDA of elemental zinc for at least a period of 14 days, introduced within one month of birth. Electronic databases were searched irrespective of language and publication status. FINDINGS Three trials from developing countries met the inclusion criteria. Limited data did not indicate a reduced risk of mortality (1 trial, RR=1.11; 95% CI 0.57 to 2.18 at one year), hospitalization rate (1 trial, odds ratio 1.10; 95% CI 0.87 to 1.39), acute respiratory infection (1 trial), or diarrhea (2 trials). However, the trial reporting on mortality was not adequately powered for evaluating this outcome. There was no evidence of an increase in weight (3 trials) or height (2 trials) at either 6 months or one year of age, or of an increased risk of vomiting following zinc supplementation. Serum zinc levels at the end of intervention were significantly higher in the supplemented group (2 trials). CONCLUSIONS In view of no convincing evidence of benefits from the limited data available, currently there is no justification for recommending routine zinc supplementation for breastfed LBW newborns in developing countries.
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Affiliation(s)
- Anjana Gulani
- Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, B-16 Qutab Institutional Area, New Delhi, India
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Patel AB, Mamtani M, Badhoniya N, Kulkarni H. What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis. BMC Infect Dis 2011; 11:122. [PMID: 21569418 PMCID: PMC3115868 DOI: 10.1186/1471-2334-11-122] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2011] [Accepted: 05/12/2011] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea. METHODS EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes. RESULTS We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity. CONCLUSIONS Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.
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Imdad A, Bhutta ZA. Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the lives saved tool. BMC Public Health 2011; 11 Suppl 3:S22. [PMID: 21501440 PMCID: PMC3231896 DOI: 10.1186/1471-2458-11-s3-s22] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Introduction Zinc plays an important role in cellular growth, cellular differentiation and metabolism. The results of previous meta-analyses evaluating effect of zinc supplementation on linear growth are inconsistent. We have updated and evaluated the available evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and tried to explain the difference in results of the previous reviews. Methods A literature search was done on PubMed, Cochrane Library, IZiNCG database and WHO regional data bases using different terms for zinc and linear growth (height). Data were abstracted in a standardized form. Data were analyzed in two ways i.e. weighted mean difference (effect size) and pooled mean difference for absolute increment in length in centimeters. Random effect models were used for these pooled estimates. We have given our recommendations for effectiveness of zinc supplementation in the form of absolute increment in length (cm) in zinc supplemented group compared to control for input to Live Saves Tool (LiST). Results There were thirty six studies assessing the effect of zinc supplementation on linear growth in children < 5 years from developing countries. In eleven of these studies, zinc was given in combination with other micronutrients (iron, vitamin A, etc). The final effect size after pooling all the data sets (zinc ± iron etc) showed a significant positive effect of zinc supplementation on linear growth [Effect size: 0.13 (95% CI 0.04, 0.21), random model] in the developing countries. A subgroup analysis by excluding those data sets where zinc was supplemented in combination with iron showed a more pronounced effect of zinc supplementation on linear growth [Weighed mean difference 0.19 (95 % CI 0.08, 0.30), random model]. A subgroup analysis from studies that reported actual increase in length (cm) showed that a dose of 10 mg zinc/day for duration of 24 weeks led to a net a gain of 0.37 (±0.25) cm in zinc supplemented group compared to placebo. This estimate is recommended for inclusion in Lives Saved Tool (LiST) model. Conclusions Zinc supplementation has a significant positive effect on linear growth, especially when administered alone, and should be included in national strategies to reduce stunting in children < 5 years of age in developing countries.
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Affiliation(s)
- Aamer Imdad
- Division of Women and Child Health, Aga Khan University, Karachi, Pakistan
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Lassi ZS, Haider BA, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2010:CD005978. [PMID: 21154362 DOI: 10.1002/14651858.cd005978.pub2] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and reduce child mortality. OBJECTIVES To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January Week 2, 2010), EMBASE (1974 to January 2010) and LILACS (1985 to January 2010). SELECTION CRITERIA Randomised controlled trials (RCTs) evaluating supplementation of zinc for the prevention of pneumonia in children aged 2 to 59 months of age. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. MAIN RESULTS We included six trials and 7850 participants in the meta-analysis. Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, fixed-effect, six studies) and prevalence of pneumonia by 41% (RR 0.59; 95% CI 0.35 to 0.99, random-effects, one study). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (RR 0.79; 95% CI 0.0.71 to 0.88, fixed-effect, four studies, n = 4591) but had no effect on lower specificity pneumonia case definition (i.e. age specific fast breathing with or without lower chest indrawing) (RR 0.95; 95% CI 0.86 to 1.06, fixed-effect, four studies, n = 3259). AUTHORS' CONCLUSIONS Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia, the leading cause of death in children.
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Affiliation(s)
- Zohra S Lassi
- Division of Women and Child Health, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi, Pakistan, 74800
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Johnston BC, Shamseer L, da Costa BR, Tsuyuki RT, Vohra S. Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review. Pediatrics 2010; 126:e222-31. [PMID: 20566617 DOI: 10.1542/peds.2009-3667] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.
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Affiliation(s)
- Bradley C Johnston
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada.
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Barros FC, Bhutta ZA, Batra M, Hansen TN, Victora CG, Rubens CE, the GAPPS Review Group. Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions. BMC Pregnancy Childbirth 2010; 10 Suppl 1:S3. [PMID: 20233384 PMCID: PMC2841444 DOI: 10.1186/1471-2393-10-s1-s3] [Citation(s) in RCA: 176] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). METHODS Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. RESULTS Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome CONCLUSION The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.
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Affiliation(s)
- Fernando C Barros
- Post-Graduate Course in Health and Behaviour, Universidade Catolica de Pelotas, Brazil
| | | | - Maneesh Batra
- Divison of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA
| | | | | | - Craig E Rubens
- Global Alliance to Prevent Prematurity and Stillbirth, an initiative of Seattle Children's, Seattle, Washington, USA
- Department of Pediatrics at University of Washington School of Medicine, Seattle, Washington, USA
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Abstract
BACKGROUND Otitis media (inflammation of the middle ear, usually caused by infection) affects people of all ages, but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. Because zinc supplements prevent pneumonia in disadvantaged children, we wondered whether they prevent otitis media. OBJECTIVES To evaluate whether zinc supplements prevent otitis media in adults and children of different ages. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2) which includes the Acute Respiratory Infection Groups' Specialised Register; MEDLINE (1950 to June Week 1 2009); and EMBASE (1974 to June 2009). SELECTION CRITERIA Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media. DATA COLLECTION AND ANALYSIS Two review authors assessed the eligibility and methodological quality of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate. MAIN RESULTS We identified 12 trials for inclusion, 10 of which contributed outcomes data. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow up (3191 participants), while another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc on the mean number of episodes of otitis media (mean difference -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events, but a small minority of children were reported to have vomited shortly after ingestion of the supplements. AUTHORS' CONCLUSIONS Evidence on whether zinc supplementation can reduce the incidence of otitis media in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus, but this is based on one small trial and should therefore be treated with caution.
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Affiliation(s)
- Katharine Abba
- International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, Merseyside, UK, L3 5QA
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Effect of oral zinc supplementation on the growth of preterm infants. Indian Pediatr 2010; 47:845-9. [PMID: 20308765 DOI: 10.1007/s13312-010-0145-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2009] [Accepted: 11/05/2009] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To compare the effect of oral zinc supplementation on growth of preterm infants. DESIGN Randomized controlled trial. SETTING Dhaka Shisu Hospital (Tertiary care hospital). SUBJECTS 100 appropriate for date preterm infants weighing between 1000 to 2500 g were randomized to receive zinc and multivitamin supplement (Group I; n=50) or only multivitamin supplement (Group II). INTERVENTION Zinc supplementation was given 2mg/kg/day for 6 weeks along with multivitamin in Group I and only multivitamin to Group II. PRIMARY OUTCOME VARIABLE Increment of weight and length. RESULTS At enrollment, serum zinc (62.1 ± 12.4 ug/dL in Group I and 63.1 ± 14.6 ug/dL in Group II) and hemoglobin levels (14.9 ± 2.4 g/dL in Group I and 14.4 ± 1.7 g/dL in Group II) were almost similar in both groups. Serum zinc levels were in lower limit of normal range. After supplementation, serum zinc and hemoglobin levels were significantly higher in Group I (105 ± 16.5 ug/dL) than Group II (82.2 ± 17.4 ug/dL) (P<0.05). Weight, length and head circumference were comparable in both groups at enrollment. Significant differences in weight gain and increment in length were found in first and second follow up between two groups but OFC increments were not significant (P>0.05). Reduction of morbidity was apparent in zinc supplemented group. No serious adverse effect was noted related to supplementation therapy. CONCLUSION Zinc supplementation for preterm low birth weight babies is found effective to enhance the growth in early months of life.
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Eneroth H, El Arifeen S, Persson LA, Kabir I, Lönnerdal B, Hossain MB, Ekström EC. Duration of exclusive breast-feeding and infant iron and zinc status in rural Bangladesh. J Nutr 2009; 139:1562-7. [PMID: 19535419 DOI: 10.3945/jn.109.104919] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
There is a concern that exclusive breast-feeding (EBF) for 6 mo may lead to iron and zinc deficiency in low-birth weight (LBW) infants. We assessed the association between duration of EBF and infant iron and zinc status in the Maternal and Infant Nutrition Interventions in Matlab trial, Bangladesh, stratified for normal birth weigh (NBW) and LBW. Duration of EBF was classified into EBF <4 mo and EBF 4-6 mo based on monthly recalls of foods introduced to the infant. Blood samples collected at 6 mo were analyzed for plasma zinc (n = 1032), plasma ferritin (n = 1040), and hemoglobin (Hb) (n = 791). Infants EBF 4-6 mo had a higher mean plasma zinc concentration (9.9 +/- 2.3 micromol/L) than infants EBF <4mo (9.5 +/- 2.0 micromol/L) (P < 0.01). This association was apparent in only the NBW strata and was not reflected in a lower prevalence of zinc deficiency. Duration of EBF was not associated with concentration of plasma ferritin, Hb concentration, or prevalence of iron deficiency or anemia in any strata. Regardless of EBF duration, the prevalence of zinc deficiency, iron deficiency, and anemia was high in infants in this population and strategies to prevent deficiency are needed.
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Affiliation(s)
- Hanna Eneroth
- International Maternal and Child Health, Department of Women's and Children's Health, Uppsala University, SE-75185 Uppsala, Sweden.
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Taneja S, Bhandari N, Rongsen-Chandola T, Mahalanabis D, Fontaine O, Bhan MK. Effect of zinc supplementation on morbidity and growth in hospital-born, low-birth-weight infants. Am J Clin Nutr 2009; 90:385-91. [PMID: 19553296 DOI: 10.3945/ajcn.2009.27707] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Low-birth-weight infants may have impaired zinc status, but little is known about the effect of zinc supplementation. OBJECTIVE The objective was to investigate the effect of daily zinc supplementation on morbidity and anthropometric status in hospital-born, low-birth-weight infants. DESIGN In a double-blind, randomized, placebo-controlled trial, 2052 hospital-born term infants with a birth weight < or =2500 g were randomly assigned to receive zinc or placebo. The zinc group received elemental zinc: 5 mg/d for those infants between ages 2 wk and 6 mo and 10 mg/d for those infants aged >6 mo. All-cause hospitalizations, prevalence of diarrhea, acute lower respiratory tract infections, visits to health care providers, weights, and lengths were ascertained at 3, 6, 9, and 12 mo of age. RESULTS The supplement was consumed for >85% of the follow-up period. Mean plasma zinc at 12 mo of age was higher in the zinc group (100.2 microg/dL) than in the control group (73.3 microg/dL) (difference in means: 26.9; 95% CI: 19.6, 34.2). The 24-h and 7-d prevalence of diarrhea and acute lower respiratory tract infections was similar at 3, 6, 9, and 12 mo. Care-seeking for illness was significantly lower in the zinc group (difference in proportions: -5.7; 95% CI: -9.9, -1.4; P < 0.05) at 9 mo. The numbers of hospitalizations, weights, and lengths were all similar at all 4 assessments. CONCLUSION Hospital-born, term, low-birth-weight infants do not seem to benefit substantially from zinc supplementation that meets the Recommended Dietary Allowance for zinc in terms of morbidity or physical growth during infancy in this setting. This trial was registered at www.clinicaltrials.gov as NCT00272142.
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Brown KH, Peerson JM, Baker SK, Hess SY. Preventive Zinc Supplementation among Infants, Preschoolers, and Older Prepubertal Children. Food Nutr Bull 2009; 30:S12-40. [DOI: 10.1177/15648265090301s103] [Citation(s) in RCA: 204] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by ∼20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by ∼15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on children's behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.
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Ramakrishnan U, Nguyen P, Martorell R. Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr 2009; 89:191-203. [PMID: 19056559 DOI: 10.3945/ajcn.2008.26862] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Micronutrient interventions have received much attention as a cost-effective and promising strategy to improve child health, but their roles in improving child growth remain unclear. OBJECTIVE Meta-analyses of randomized controlled trials were conducted to evaluate the effect of micronutrient interventions on the growth of children aged <5 y old. DESIGN Eligible studies were identified by PubMed database searches and other methods. Weighted mean effect sizes and 95% CIs were calculated for changes in height, weight, and weight-for-height z scores (WHZ) by using random-effect models. Tests for publication bias were done by using funnel plots, heterogeneity, and stratified analyses by predefined characteristics. RESULTS Interventions including iron (n = 27) or vitamin A (n = 17) only had no significant effects on growth. Interventions including zinc only (n = 43) had a small positive effect (effect size = 0.06; 95% CI: 0.006, 0.11) on change in WHZ but no significant effect on height or weight gain. Multiple micronutrient interventions (n = 20) improved linear growth (0.09; 95% CI: 0.008, 0.17). CONCLUSIONS Our findings confirm earlier results of no benefits for interventions including iron and vitamin A only but differ from the earlier meta-analysis that found improvements in linear growth for zinc only interventions. This may be due to the improved nutritional status of children in the more recent studies. Multiple micronutrient interventions improve linear growth, but the benefits are small. Other strategies are needed to prevent stunting.
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Affiliation(s)
- Usha Ramakrishnan
- Nutrition and Health Sciences Program and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
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Abstract
BACKGROUND Diarrhoea causes around two million child deaths annually. Zinc supplementation could help reduce the duration and severity of diarrhoea, and is recommended by the World Health Organization and UNICEF. OBJECTIVES To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH STRATEGY In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA Randomized controlled trials comparing oral zinc supplementation (>/= 5 mg/day for any duration) with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS Both authors assessed trial eligibility and methodological quality, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity. MAIN RESULTS Eighteen trials enrolling 6165 participants met our inclusion criteria. In acute diarrhoea, zinc resulted in a shorter diarrhoea duration (MD -12.27 h, 95% CI -23.02 to -1.52 h; 2741 children, 9 trials), and less diarrhoea at day three (RR 0.69, 95% CI 0.59 to 0.81; 1073 children, 2 trials), day five (RR 0.55, 95% CI 0.32 to 0.95; 346 children, 2 trials), and day seven (RR 0.71, 95% CI 0.52 to 0.98; 4087 children, 7 trials). The four trials (1458 children) that reported on diarrhoea severity used different units and time points, and the effect of zinc was less clear. Subgroup analyses by age (trials with only children aged less than six months) showed no benefit with zinc. Subgroup analyses by nutritional status, geographical region, background zinc deficiency, zinc type, and study setting did not affect the results' significance. Zinc also reduced the duration of persistent diarrhoea (MD -15.84 h, 95% CI -25.43 to -6.24 h; 529 children, 5 trials). Few trials reported on severity, and results were inconsistent. No trial reported serious adverse events, but vomiting was more common in zinc-treated children with acute diarrhoea (RR 1.71, 95% 1.27 to 2.30; 4727 children, 8 trials). AUTHORS' CONCLUSIONS In areas where diarrhoea is an important cause of child mortality, research evidence shows zinc is clearly of benefit in children aged six months or more.
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Affiliation(s)
- Marzia Lazzerini
- Unit of Research on Health Services and International Health, WHO Collaborating Centre for Maternal and Child Health, Via dei Burlo 1,34123, Trieste, Italy.
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Global and regional child mortality and burden of disease attributable to zinc deficiency. Eur J Clin Nutr 2008; 63:591-7. [PMID: 18270521 DOI: 10.1038/ejcn.2008.9] [Citation(s) in RCA: 113] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND/OBJECTIVES Zinc is an essential micronutrient and deficiency can lead to an increased risk for infectious diseases and growth retardation among children under 5 years of age. We aimed to estimate disease-specific and all-cause mortality attributable to zinc deficiency. SUBJECT/METHODS We estimated the prevalence of zinc deficiency in Latin America, Africa and Asia, where based on zinc availability in the diet and childhood stunting rates, zinc deficiency is widespread. The relative risks of death among zinc-deficient children for diarrhea, malaria and pneumonia were estimated from randomized controlled trials. We used the comparative risk assessment methods to calculate deaths and burden of disease (measured in disability-adjusted life years, DALYs) from each of these three diseases attributable to zinc deficiency in these regions. RESULTS Zinc deficiency was responsible for 453,207 deaths (4.4% of childhood deaths), and 1.2% of the burden of disease (3.8% among children between 6 months and 5 years) in these three regions in 2004. Of these deaths, 260,502 were in Africa, 182,546 in Asia and 10,159 in Latin America. Zinc deficiency accounted for 14.4% of diarrhea deaths, 10.4% of malaria deaths and 6.7% of pneumonia deaths among children between 6 months and 5 years of age. CONCLUSIONS Zinc deficiency contributes to substantial morbidity and mortality, especially from diarrhea. Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency.
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Abstract
Zinc is an essential micronutrient for growth and proper immune function. There is currently no simple recommendation for the assessment of population-level zinc deficiency. Trials of zinc supplementation have shown positive effects of supplementation on clinical outcomes and growth. We reviewed the results of randomized trials of zinc supplementation and correlation studies that assessed infectious diseases, growth, and development outcomes among children under 5 years of age. The results indicate that zinc supplementation decreases the incidence and prevalence of diarrhea and pneumonia, but the use of trial data to make population-level estimates of zinc deficiency is not practical and is difficult to quantify. The data also indicate that zinc supplementation increases growth, especially among children who are stunted. Stunting rates are commonly estimated and can be used to estimate zinc deficiency. Previous recommendations suggest that stunting rates at or above 20% should be indicative of zinc deficiency among children under 5 years of age. This review provides additional data and analysis to support the current recommendation.
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Affiliation(s)
- Christa L Fischer Walker
- Johns Hopkins University Bloomberg School of Public Health, Department of International Health, Baltimore, Maryland 21205, USA.
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Luabeya KKA, Mpontshane N, Mackay M, Ward H, Elson I, Chhagan M, Tomkins A, den Broeck JV, Bennish ML. Zinc or multiple micronutrient supplementation to reduce diarrhea and respiratory disease in South African children: a randomized controlled trial. PLoS One 2007; 2:e541. [PMID: 17593956 PMCID: PMC1891438 DOI: 10.1371/journal.pone.0000541] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2007] [Accepted: 05/09/2007] [Indexed: 11/23/2022] Open
Abstract
Background Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain. Objective To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence. Design Randomized, double-blind, controlled trial. Setting Rural community in South Africa. Participants Three cohorts: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers. Interventions Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly. Outcome Measures Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker. Results Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts. Conclusion When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children. Trial Registration ClinicalTrials.gov NCT00156832
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Affiliation(s)
| | | | - Malanie Mackay
- Department of Medical Microbiology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Honorine Ward
- Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Centre, Boston, Massachusetts, United States of America
| | - Inga Elson
- Department of Chemical Pathology, University of KwaZulu-Natal, Durban, South Africa
| | - Meera Chhagan
- Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America
| | - Andrew Tomkins
- Centre for International Child Health, University of London, London, United Kingdom
| | - Jan Van den Broeck
- Tropical Medicine Research Institute, University of the West Indies, Kingston, Jamaica
| | - Michael L. Bennish
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
- * To whom correspondence should be addressed. E-mail:
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Aggarwal R, Sentz J, Miller MA. Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: a meta-analysis. Pediatrics 2007; 119:1120-30. [PMID: 17545379 DOI: 10.1542/peds.2006-3481] [Citation(s) in RCA: 167] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The quantified effect of zinc supplementation to prevent childhood diarrhea and respiratory illnesses is unclear. We conducted a meta-analysis of randomized, controlled trials on the subject. METHODS We searched PubMed, Science Citation Index, and the Cochrane Database of Controlled Trials and hand-searched the reference lists of identified articles. All randomized, controlled trials of zinc supplementation for > or = 3 months for children < 5 years of age, using blinded assessment, were eligible. The outcome measures studied were number of episodes of illness, number of days with illness, and number of episodes of severe illness. Data from 17 studies were pooled by using random-effects and fixed-effects models for data with and without significant heterogeneity, respectively. RESULTS Children who received a zinc supplement had fewer episodes of diarrhea (rate ratio: 0.86) and respiratory tract infections (rate ratio: 0.92) and significantly fewer attacks of severe diarrhea or dysentery (rate ratio: 0.85), persistent diarrhea (rate ratio: 0.75), and lower respiratory tract infection or pneumonia (rate ratio: 0.80) than did those who received placebo. They also had significantly fewer total days with diarrhea (rate ratio: 0.86) but not days with respiratory illness (rate ratio: 0.95). Published studies showed a publication bias and significant heterogeneity; however, no cause for the latter could be identified. CONCLUSIONS Zinc supplementation reduced significantly the frequency and severity of diarrhea and respiratory illnesses and the duration of diarrheal morbidity. The relatively limited reduction in morbidity and the presence of significant heterogeneity and of publication bias indicate the need for larger, high-quality studies to identify subpopulations most likely to benefit.
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Affiliation(s)
- Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Dehbozorgi P, . PM, . ZM. The Influence of Zinc Sulfate Supplementation on the Growth of School Age Children in Villages Around Shiraz 2002, 2003. JOURNAL OF MEDICAL SCIENCES 2007. [DOI: 10.3923/jms.2007.690.693] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Walker CLF, Bhutta ZA, Bhandari N, Teka T, Shahid F, Taneja S, Black RE. Zinc during and in convalescence from diarrhea has no demonstrable effect on subsequent morbidity and anthropometric status among infants <6 mo of age. Am J Clin Nutr 2007; 85:887-94. [PMID: 17344513 DOI: 10.1093/ajcn/85.3.887] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Preventing illness and improving growth in the first 6 mo of life is critical to reducing infant mortality. Zinc given for 14 d at the start of diarrhea has been shown to decrease the incidence and prevalence of diarrhea and pneumonia and improve growth in the 2-3 mo after, but no trial has been done in infants <6 mo of age. OBJECTIVE This study sought to assess the effect of 14 d of zinc supplementation on subsequent morbidity and growth among infants 1-5 mo of age living in Pakistan, India, and Ethiopia. DESIGN Infants with acute diarrhea were randomly assigned to receive zinc (10 mg/d; n = 538) or placebo (n = 536) for 2 wk. Weekly follow-up visits were conducted for 8 wk after the diarrhea episode. Incidence and prevalence of diarrhea and prevalence of respiratory infections including pneumonia were compared between the groups. Changes in weight, length, and corresponding z scores during the 8 wk of follow-up were also compared. RESULTS One thousand seventy-four infants were enrolled at the start of follow-up. The groups did not differ significantly in the proportion of infants with at least one episode of diarrhea or respiratory infections. Infants who received zinc had more days of diarrhea (rate ratio = 1.20) than did the infants who received placebo. The groups had similar prevalences of pneumonia and overall respiratory infections. No significant differences in the mean changes in weight-for-age, length-for-age, and weight-for-length z scores were observed between the groups overall or in stratified analyses. CONCLUSION Young infants do not appear to benefit from 2 wk of zinc, unlike what has been observed among older children.
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Affiliation(s)
- Christa L Fischer Walker
- Johns Hopkins Bloomberg School of Public Health, Department of International Health, Baltimore, MD 21218, USA.
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