Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age.

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.

Food fortification with multiple micronutrients: impact on health outcomes in general population.

BACKGROUND: Vitamins and minerals are essential for growth and maintenance of a healthy body, and have a role in the functioning of almost every organ. Multiple interventions have been designed to improve micronutrient deficiency, and food fortification is one of them. OBJECTIVES: To assess the impact of food fortification with multiple micronutrients on health outcomes in the general population, including men, women and children. SEARCH METHODS: We searched electronic databases up to 29 August 2018, including the Cochrane Central Register of Controlled Trial (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register and Cochrane Public Health Specialised Register; MEDLINE; Embase, and 20 other databases, including clinical trial registries. There were no date or language restrictions. We checked reference lists of included studies and relevant systematic reviews for additional papers to be considered for inclusion. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, quasi-randomised trials, controlled before-after (CBA) studies and interrupted time series (ITS) studies that assessed the impact of food fortification with multiple micronutrients (MMNs). Primary outcomes included anaemia, micronutrient deficiencies, anthropometric measures, morbidity, all-cause mortality and cause-specific mortality. Secondary outcomes included potential adverse outcomes, serum concentration of specific micronutrients, serum haemoglobin levels and neurodevelopmental and cognitive outcomes. We included food fortification studies from both high-income and low- and middle-income countries (LMICs). DATA COLLECTION AND ANALYSIS: Two review authors independently screened, extracted and quality-appraised the data from eligible studies. We carried out statistical analysis using Review Manager 5 software. We used random-effects meta-analysis for combining data, as the characteristics of study participants and interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables, using the GRADE approach. MAIN RESULTS: We identified 127 studies as relevant through title/abstract screening, and included 43 studies (48 papers) with 19,585 participants (17,878 children) in the review. All the included studies except three compared MMN fortification with placebo/no intervention. Two studies compared MMN fortification versus iodised salt and one study compared MMN fortification versus calcium fortification alone. Thirty-six studies targeted children; 20 studies were conducted in LMICs. Food vehicles used included staple foods, such as rice and flour; dairy products, including milk and yogurt; non-dairy beverages; biscuits; spreads; and salt. Fourteen of the studies were fully commercially funded, 13 had partial-commercial funding, 14 had non-commercial funding and two studies did not specify the source of funding. We rated all the evidence as of low to very low quality due to study limitations, imprecision, high heterogeneity and small sample size. When compared with placebo/no intervention, MMN fortification may reduce anaemia by 32% (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.56 to 0.84; 11 studies, 3746 participants; low-quality evidence), iron deficiency anaemia by 72% (RR 0.28, 95% CI 0.19 to 0.39; 6 studies, 2189 participants; low-quality evidence), iron deficiency by 56% (RR 0.44, 95% CI 0.32 to 0.60; 11 studies, 3289 participants; low-quality evidence); vitamin A deficiency by 58% (RR 0.42, 95% CI 0.28 to 0.62; 6 studies, 1482 participants; low-quality evidence), vitamin B2 deficiency by 64% (RR 0.36, 95% CI 0.19 to 0.68; 1 study, 296 participants; low-quality evidence), vitamin B6 deficiency by 91% (RR 0.09, 95% CI 0.02 to 0.38; 2 studies, 301 participants; low-quality evidence), vitamin B12 deficiency by 58% (RR 0.42, 95% CI 0.25 to 0.71; 3 studies, 728 participants; low-quality evidence), weight-for-age z-scores (WAZ) (mean difference (MD) 0.1, 95% CI 0.02 to 0.17; 8 studies, 2889 participants; low-quality evidence) and weight-for-height/length z-score (WHZ/WLZ) (MD 0.1, 95% CI 0.02 to 0.18; 6 studies, 1758 participants; low-quality evidence). We are uncertain about the effect of MMN fortification on zinc deficiency (RR 0.84, 95% CI 0.65 to 1.08; 5 studies, 1490 participants; low-quality evidence) and height/length-for-age z-score (HAZ/LAZ) (MD 0.09, 95% CI 0.01 to 0.18; 8 studies, 2889 participants; low-quality evidence). Most of the studies in this comparison were conducted in children. Subgroup analyses of funding sources (commercial versus non-commercial) and duration of intervention did not demonstrate any difference in effects, although this was a relatively small number of studies and the possible association between commercial funding and increased effect estimates has been demonstrated in the wider health literature. We could not conduct subgroup analysis by food vehicle and funding; since there were too few studies in each subgroup to draw any meaningful conclusions. When we compared MMNs versus iodised salt, we are uncertain about the effect of MMN fortification on anaemia (R 0.86, 95% CI 0.37 to 2.01; 1 study, 88 participants; very low-quality evidence), iron deficiency anaemia (RR 0.40, 95% CI 0.09 to 1.83; 2 studies, 245 participants; very low-quality evidence), iron deficiency (RR 0.98, 95% CI 0.82 to 1.17; 1 study, 88 participants; very low-quality evidence) and vitamin A deficiency (RR 0.19, 95% CI 0.07 to 0.55; 2 studies, 363 participants; very low-quality evidence). Both of the studies were conducted in children. Only one study conducted in children compared MMN fortification versus calcium fortification. None of the primary outcomes were reported in the study. None of the included studies reported on morbidity, adverse events, all-cause or cause-specific mortality. AUTHORS' CONCLUSIONS: The evidence from this review suggests that MMN fortification when compared to placebo/no intervention may reduce anaemia, iron deficiency anaemia and micronutrient deficiencies (iron, vitamin A, vitamin B2 and vitamin B6). We are uncertain of the effect of MMN fortification on anthropometric measures (HAZ/LAZ, WAZ and WHZ/WLZ). There are no data to suggest possible adverse effects of MMN fortification, and we could not draw reliable conclusions from various subgroup analyses due to a limited number of studies in each subgroup. We remain cautious about the level of commercial funding in this field, and the possibility that this may be associated with higher effect estimates, although subgroup analysis in this review did not demonstrate any impact of commercial funding. These findings are subject to study limitations, imprecision, high heterogeneity and small sample sizes, and we rated most of the evidence low to very low quality. and hence no concrete conclusions could be drawn from the findings of this review.

Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months.

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.

Vulnerable road users are at greater risk during Ramadan -- results from road traffic surveillance data.

OBJECTIVE: To assess how the frequency, nature and outcome of road traffic crashes differ during the fasting month of Ramadan. METHODS: The retrospective study was conducted in Karachi and comprised data from the Road Traffic Injury Surveillance Project which entailed information on all road traffic injury victims presenting to Emergency Departments in the city between September 2006 and September 2011. Data was analysed to find the frequency of road traffic crashes according to time of incident, road user group and survival. Ramadan and Non-Ramadan groups were compared with respect to time and frequency of incidents, road user group and mortality. SPSS 16 was used for statistical analysis. RESULTS: There were 163,022 subjects from whom 13,640(8.36%) came during Ramadan and 149,382 (91.6%) during the non-Ramadan months. Frequency of road traffic crashes did not change significantly during Ramadan, but was clustered around the breaking of Fast and the Taravih prayers. The most commonly affected road user group was motorbike riders followed by pedestrians. Overall survival of the RTI victims was 96.1% with a mortality rate of 4.1% which was higher than the figure of 3.5% in the non-Ramadan period. CONCLUSIONS: Vulnerable road users were more frequently involved in road traffic injuries during Ramadan. Moreover, the frequency of crashes increased around evening which requires more careful planning of traffic controls, especially for the vulnerable road users.

Adherence to the 2017 Clinical Practice Guidelines for Pediatric Hypertension in Safety-Net Clinics.

Importance: The 2017 Clinical Practice Guideline (CPG) for the diagnosis and management of pediatric hypertension (PHTN) categorizes a greater proportion of children with elevated blood pressure and PHTN, yet several barriers to CPG adherence have been noted. Objective: To assess adherence to the 2017 CPG for the diagnosis and management of PHTN and use of a clinical decision support (CDS) tool to calculate blood pressure percentiles. Design, Setting, and Participants: This cross-sectional study used electronic health record-extracted data from January 1, 2018, to December 31, 2019, among patients visiting 1 of 74 federally qualified health centers in AllianceChicago, a national Health Center Controlled Network. Children and adolescents (aged 3-17 years; hereinafter referred to as children) who attended at least 1 visit and had at least 1 blood pressure reading at or above the 90th percentile or diagnosis of elevated blood pressure or PHTN were eligible for data to be included in the analysis. Data were analyzed from September 1, 2020, to February 21, 2023. Exposures: Blood pressure at or above the 90th or 95th percentile. Main Outcomes and Measures: Diagnosis of PHTN (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], code I10) or elevated blood pressure (ICD-10 code R03.0) and CDS tool use; blood pressure management (antihypertensive medication, lifestyle counseling, referral); and follow-up visit attendance. Descriptive statistics described the sample and rates of guideline adherence. Logistic regression analyses identified patient- and clinic-level associations with guideline adherence. Results: The sample consisted of 23 334 children (54.9% boys; 58.6% White race; median age, 8 [IQR, 4-12] years). Guideline-adherent diagnosis was observed in 8810 children (37.8%) with blood pressure at or above the 90th percentile and 146 of 2542 (5.7%) with blood pressure at or above the 95th percentile at 3 or more visits. The CDS tool was used to calculate blood pressure percentiles in 10 524 cases (45.1%) and was associated with significantly greater odds of PHTN diagnosis (odds ratio, 2.14 [95% CI, 1.10-4.15]). Among 15 422 children with blood pressure at or above the 95th percentile, antihypertensive medication was prescribed to 831 (5.4%), lifestyle counseling was provided to 14 841 (96.2%), and blood pressure-related referrals were given to 848 (5.5%). Guideline-adherent follow-up was observed in 8651 of 19 049 children (45.4%) with blood pressure at or above the 90th percentile and 2598 of 15 164 (17.1%) with blood pressure at or above the 95th percentile. Differences in guideline adherence by patient- and clinic-level factors were observed. Conclusions and Relevance: In this study, fewer than 50% of children with elevated blood pressure had a guideline-adherent diagnosis code or attended guideline-adherent follow-up. Using a CDS tool was associated with guideline-adherent diagnosis, but the tool was underused. Further work is needed to understand how to best support implementation of tools promoting PHTN diagnosis, management, and follow-up.

Under-recognition of pediatric hypertension diagnosis: Examination of 1 year of visits to community health centers.

Pediatric hypertension is associated with significant target organ damage in children and cardiovascular morbidity in adulthood. Appropriate diagnosis and management per guideline recommendations are inconsistent. In this study, we determined the proportion of missed diagnosis of hypertension and prehypertension and appropriate follow-up in pediatric patients, stratified by sex, age, race/ethnicity, and weight status. Based on the electronic health record (EHR) data from eight federally qualified health centers, among 62,982 children aged 3 to 18 years, 6233 (10%) had at least one abnormal blood pressure (BP) measurement over twelve months. Among those children whose recorded BPs met the criteria for prehypertension (N = 6178), 14.6% had a diagnosis in the EHR. These children were more likely to be White and have obesity compared with children who met the criteria but were not diagnosed with prehypertension. Among those who met the criteria for hypertension (N = 55), 41.8% had a diagnosis of hypertension in the EHR. Being diagnosed with hypertension was not associated with any examined patient characteristics. Over eleven months, 2837 children had BP ≥ 95th percentile on ≥ 1 visit. Only 13% had guideline-adherent follow-up within 1 month and were more likely to be older, female, and of Hispanic ethnicity or "other" race. Over six months, 2902 children had BP ≥ 90th percentile on one visit. 41% had guideline-adherent follow-up within 6 months and were more likely to be older, of either White, Hispanic, Asian race, or Hispanic ethnicity. In a community-based setting, pediatric hypertension and prehypertension were persistently underdiagnosed with low adherence to recommended follow-up.

Systematic review on evidence-based adolescent nutrition interventions.

Adolescence is a critical stage in the life cycle, and adequate nutrition is necessary for the proper growth and development of individuals and their offspring. Here, we comprehensively review all published systematic reviews (through October 2016) on adolescents (10-19 years) and women of reproductive age, including pregnant women, which targeted interventions related to nutrition. For interventions where there was no existing systematic review on adolescents, we reviewed primary studies/trials. We included interventions on micronutrient supplementation (iron, folic acid, iron-folic acid (IFA), calcium, vitamin D, vitamin A, zinc, iodine, and multiple micronutrients), food/protein energy supplementation, nutrition education for pregnant adolescents, obesity prevention and management, and management of gestational diabetes. We identified a total of 35 systematic reviews, of which only five were conducted on adolescents, and 107 primary studies on adolescents. Our review suggests that iron alone, IFA, zinc, and multiple micronutrient supplementation in adolescents can significantly improve serum hemoglobin concentration. While zinc supplementation in pregnant adolescents showed improvements in preterm birth and low birth weight, we found a paucity of trials on calcium, vitamin D, vitamin A, and iodine supplementation. We found limited evidence on food/protein energy supplementation in adolescents. Interventions to prevent and manage obesity showed a nonsignificant impact on reducing body mass index. This review underscores the importance of adolescent nutrition interventions. It is imperative that countries design nutritional interventions, particularly for adolescents.

Can routine screening and iron supplementation for iron deficiency anemia in nonsymptomatic pregnant women improve maternal and infant health outcomes?

Pregnant women have an increased need for iron that might not be met with diet alone. Due to physiologic anemia and population differences, no set criteria for defining iron deficiency anemia (IDA) are available globally. Serum ferritin and transferrin levels are often used to guide therapy by clinicians. Studies have reported an association between poor iron status and negative health outcomes such as low birth weight, premature birth, and perinatal death for women and their infants, although the evidence is weak.

Functional, cognitive and psychological outcomes, and recurrent vascular events in Pakistani stroke survivors: a cross sectional study.

BACKGROUND: There is little direct data describing the outcomes and recurrent vascular morbidity and mortality of stroke survivors from low and middle income countries like Pakistan. This study describes functional, cognitive and vascular morbidity and mortality of Pakistani stroke survivors discharged from a dedicated stroke center within a nonprofit tertiary care hospital based in a multiethnic city with a population of more than 20 million. METHODS: Patients with stroke, aged > 18 years, discharged alive from a tertiary care centre were contacted via telephone and a cross sectional study was conducted. All the discharges were contacted. Patients or their legal surrogate were interviewed regarding functional, cognitive and psychological outcomes and recurrent vascular events using standardized, pretested and translated scales. A verbal autopsy was carried out for patients who had died after discharge. Stroke subtype and risk factors data was collected from the medical records. Subdural hemorrhages, traumatic ICH, subarachnoid hemorrhage, iatrogenic stroke within hospital and all other diagnoses that presented like stroke but were subsequently found not to have stroke were also excluded. Composites were created for functional outcome variable and depression. Data were analyzed using logistic regression. RESULTS: 309 subjects were interviewed at a median of 5.5 months post discharge. 12.3% of the patients had died, mostly from recurrent vascular events or stroke complications. Poor functional outcome defined as Modified Rankin Score (mRS) of > 2 and a Barthel Index (BI) score of < 90 was seen in 51%. Older age (Adj-OR-2.1, p = 0.01), moderate to severe dementia (Adj-OR-19.1, p < 0.001), Diabetes (Adj-OR-2.1, p = 0.02) and multiple post stroke complications (Adj-OR-3.6, p = 0.02) were independent predictors of poor functional outcome. Cognitive outcomes were poor in 42% and predictors of moderate to severe dementia were depression (Adj-OR-6.86, p < 0.001), multiple post stroke complications (Adj-OR-4.58, p = 0.01), presence of bed sores (Adj-OR-17.13, p = 0.01) and history of atrial fibrillation (Adj-OR-5.12, p < 0.001). CONCLUSIONS: Pakistani stroke survivors have poor outcomes in the community, mostly from preventable complications. Despite advanced disability, the principal caretakers were family rarely supported by health care personnel, highlighting the need to develop robust home care support for caregivers in these challenging resource poor settings.