Improved adherence and anaemia cure rates with flexible administration of micronutrient Sprinkles: a new public health approach to anaemia control.

BACKGROUND/OBJECTIVES: Despite repeated public commitments and availability of various forms of iron supplements, rates of anaemia in developing countries remain high. A major reason for this lack of success has been poor adherence. The objective of this study was to compare the effectiveness of daily and flexible administration of micronutrient Sprinkles on adherence, acceptability and haematological status among young children in rural Bangladesh. SUBJECTS/METHODS: A sample of 362 children (haemoglobin (Hb)>or=70 g l(-1)) aged 6-24 months were cluster-randomized to receive 60 sachets of Sprinkles either (i) daily over 2 months; (ii) flexibly over 3 months; or (iii) flexibly over 4 months. With a flexible regimen, mothers/caregivers decided how frequently to use Sprinkles without exceeding one sachet per day. Adherence was assessed monthly by counting the number of sachets used and acceptability was evaluated through focus group discussions. Haemoglobin was measured at baseline, at the end of each intervention period and 6 months post-intervention. RESULTS: Mean percent adherence was significantly higher in the flexible-4-month group (98%) compared to the flexible-3-month (93%) and daily-2-month (88%) groups (P<0.01). Most mothers found flexible administration to be more acceptable than daily due to perceived benefits of use. Hb at the end of intervention was significantly higher in the flexible-4-month group compared to the daily group (P=0.03). Anaemia prevalence decreased by 65% in the flexible-4-month group compared to 54% in the flexible-3-month and 51% in the daily-2-month groups. Percent of cured children who maintained a non-anaemic status 6 months post-intervention was significantly higher in the flexible-4-month (82%) and flexible-3-month (80%) groups than the daily-2-month (53%) group (P<0.05). CONCLUSIONS: The adherence, acceptability and haematological response to flexible administration over 4 months were found preferable to daily.

Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease.

BACKGROUND: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease. OBJECTIVES: To systematically review the efficacy and safety of n-3 for maintaining remission in Crohn's disease (CD). SEARCH STRATEGY: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was relapse rate and secondary outcomes were change in disease activity scores, time to first relapse and adverse events. DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. Meta-analysis was performed using RevMan 4.2 software, weighted by the Mantel-Haenszel method. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed to address heterogeneity. MAIN RESULTS: Four studies were eligible for inclusion. There was a non statistically significant benefit of n-3 therapy for maintaining remission (RR 0.64; 95%CI 0.4 to 1.03; P = 0.07). However, the studies were both clinically and statistically heterogeneous (P = 0.01, I(2) = 72%). Three studies used enteric coated capsules (positive effects) and one ordinary gelatin capsules (no advantage). Subgroup analyses of studies which used enteric coated capsules revealed a statistically significant benefit for maintenance of remission (RR 0.49; 95% CI 0.35 to 0.69; RD 0.31; 95% CI 0.19 to 0.43); number needed to treat to prevent relapse in 1 year was 3 (95% CI 2 to 5; I(2) = 19%). However, the total number of patients enrolled in these studies was small (n = 166). No significant adverse events were recorded in any of the studies and not enough data were available to analyze the other secondary outcomes. AUTHORS' CONCLUSIONS: Omega 3 fatty acids are safe and may be effective for maintenance of remission in CD when used in enteric coated capsules. However, there are not sufficient data to recommend the routine use of n-3 for maintenance of remission in CD. The small number of patients in the included studies warrants further larger RCTs.

Dual fortification of salt with iron and iodine in women and children in rural Ghana.

OBJECTIVE: To test the efficacy of double-fortified salt (DFS) on the anaemia and iodine deficiency (ID) status of women and their children. DESIGN: Double-blind randomised controlled trial. SETTING: Sekyere West District of Ghana. SUBJECTS: In this eight-month trial, mildly anaemic or non-anaemic, non-pregnant, non-lactating women were randomised into three groups receiving: DFS plus weekly placebo (n = 61); iodised salt plus weekly 70 mg iron supplement (n = 65); or iodised salt (IS) plus weekly placebo (control group, n = 58). Correspondingly, their mildly anaemic and non-anaemic children aged 1-5 years were randomised into two groups receiving either the DFS (n = 23) or IS alone (control group, n = 59). RESULTS: At the end of the intervention, prevalence of anaemia in women remained unchanged in the DFS or IS plus weekly iron supplement group, but significantly increased by 19.5% in the control group (P = 0.039). In children, prevalence of anaemia in the DFS group significantly decreased by 21.7% (P = 0.025) while no change was observed in the control group. ID decreased significantly in all groups of women (P < 0.001) and children (P < 0.05), with no difference among groups of women and children. CONCLUSION: While the use of DFS prevented anaemia in women, it had a significant role in both the prevention and treatment of anaemia in children. Both the DFS and IS significantly reduced ID in women and children to a similar degree.

Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan Sprinkles Diarrhoea Study.

AIMS: To examine the effect of the daily use of micronutrients (including zinc) or the same micronutrients plus heat inactivated lactic acid bacteria (LAB), on diarrhoea in children compared to placebo. METHODS: A triple blind randomised clinical trial in an urban slum of Karachi, Pakistan. Micronutrients (including zinc), micronutrients (including zinc and LAB), or placebo, were provided daily for two months to 75 young children (aged 6-12 months) identified at high risk for diarrhoea related mortality on the basis of history of at least one episode of diarrhoea in the preceding two weeks. The longitudinal prevalence of diarrhoea was defined as the percentage of days a child had diarrhoea out of the days the child was observed. RESULTS: Mean longitudinal prevalence of diarrhoea in the micronutrient-zinc group was 15% (SD = 10%) child-days compared to 26% (SD = 20%) child-days in the placebo group and 26% (SD = 19%) child-days in the micronutrient-zinc-LAB group. The difference between the micronutrient-zinc-LAB and placebo groups was not significant. CONCLUSION: The daily provision of micronutrients (including zinc) reduces the longitudinal prevalence of diarrhoea and thus may also reduce diarrhoea related mortality in young children; heat inactivated LAB has negative effects in these children.

Vitamin K deficiency in children pre-bone marrow transplantation.

This study examined the prevalence of vitamin K deficiency in children pre-bone marrow transplantation (BMT). Vitamin K status was measured by the PIVKA-II assay and prothrombin times. Blood samples were obtained before vitamin-containing TPN was infused. Results indicated that eight of 26 patients (31%) were vitamin K deficient; four cases were attributed to drug antagonism (phenytoin) and four were due to inadequate vitamin K intake, synthesis or malabsorption. Only one patient had a prolonged prothrombin time. Prothrombin time, in our study, is shown to be an ineffective screening tool to determine vitamin K status. All patients receiving phenytoin and chemotherapy are at increased risk of vitamin K deficiency.

Children's understanding of the risks and benefits associated with research.

OBJECTIVE: The objective of the current study was to maximise the amount of information children and adolescents understand about the risks and benefits associated with participation in a biomedical research study. DESIGN: Participants were presented with one of six hypothetical research protocols describing how to fix a fractured thigh using either a "standard" cast or "new" pins procedure. Risks and benefits associated with each of the treatment options were manipulated so that for each one of the six protocols there was either a correct or ambiguous choice. PARTICIPANTS AND SETTING: Two hundred and fifty one children, ages 6-15 (53% boys), and 237 adults (30% men) were interviewed while waiting for a clinic appointment at the Hospital for Sick Children. RESULTS: Using standardised procedures and questionnaires, it was determined that most participants, regardless of age group, were able to understand the basic purpose and procedures involved in the research, and most were able to choose the "correct" operation. The younger children, however, showed an overall preference for a cast operation, whereas the older participants were more likely to choose the pins. CONCLUSIONS: By creating age appropriate modules of information, children as young as six years can understand potentially difficult and complex concepts such as the risks and benefits associated with participation in biomedical research. It appears, however, that different criteria were used for treatment preference, regardless of associated risks; older participants tended to opt for mobility (the pins procedure) whereas younger participants stayed with the more familiar cast operation.

Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods.

BACKGROUND: Standard therapy for anemia in infants is ferrous sulfate drops administered 3 times/d. Adherence to treatment, however, is often poor. One likely reason for poor adherence is the unpleasant side effects associated with drops. OBJECTIVE: The objective was to evaluate the use of a new form of iron and a delivery system to treat anemia in infants that is likely to produce better adherence to treatment. DESIGN: Using a prospective, randomized, controlled design, we studied 557 anemic children aged 6-18 mo (hemoglobin: 70-99 g/L) in rural Ghana. One group received a daily sachet of microencapsulated ferrous fumarate (80 mg elemental Fe) in powder form plus ascorbic acid to be sprinkled onto any complementary food eaten (sprinkles group); a control group received ferrous sulfate drops 3 times/d for 2 mo (total dose: 40 mg elemental Fe). Hemoglobin and serum ferritin concentrations were measured at baseline and at the end of treatment. RESULTS: Successful treatment of anemia (hemoglobin > 100 g/L) occurred in 58% of the sprinkles group and in 56% of the drops group, with minimal side effects in both groups. Geometric mean ferritin concentrations increased significantly in each group from baseline to the end of treatment (P < 0.001). CONCLUSION: Use of ferrous sulfate drops or a single daily dose of microencapsulated ferrous fumarate sprinkles plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects. To our knowledge, this is the first demonstration of the use of microencapsulated iron sprinkles to treat anemia. Improved ease of use may favor the use of sprinkles to deliver iron.

Randomized, controlled trial of single versus 3-times-daily ferrous sulfate drops for treatment of anemia.

OBJECTIVE: Adherence to treatment of iron-deficiency anemia often is poor in both developed and developing countries. The current standard therapy is ferrous sulfate drops (or syrup) administered 3 times daily. It is possible that adherence would improve with a single-dose daily treatment regimen. We compared the use of single versus 3-times-daily ferrous sulfate drops, at the same total iron dose, on treatment of anemia in infants. METHODS: To obtain a large enough cohort of anemic subjects, we performed the study in rural Ghana. Using a prospective, randomized, controlled design, we studied 557 anemic children (age range: 6-24 months; hemoglobin values: 70-99 g/L). One group (n = 280) received ferrous sulfate drops once daily (40 mg elemental iron), and the control group (n = 277) received ferrous sulfate drops 3 times per day (total dose, 40 mg elemental iron). Treatment lasted for 2 months. Hemoglobin and serum ferritin values were measured at baseline and at the end of the study. RESULTS: Successful treatment of anemia (hemoglobin >100 g/L) occurred in 61% of the single-dose and in 56% of the 3-times-daily group. Geometric mean ferritin levels increased significantly in each group from baseline to the final visit. Side effects were minimal and similar between the 2 groups. CONCLUSION: A single versus a 3-times-daily dose of ferrous sulfate drops over 2 months resulted in a similar rate of successful treatment of anemia, without side effects. To our knowledge, this is the first demonstration of the use of a single-dose daily regimen to treat anemia. Although not examined in the current study, use of a single-dose daily regimen may improve adherence to treatment of anemia in infants.

An orange a day keeps the doctor away: scurvy in the year 2000.

Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.

Fractional zinc absorption using a single isotope tracer.

BACKGROUND: Fractional absorption of zinc (Zn) has been measured using dual isotopes of Zn given simultaneously. An oral test dose and an intravenous (i.v.) reference dose are administered, followed by the measurement of the double isotopic enrichment (E) in urine 48 h after administration. We postulated that an estimate of the %E in urine for a given i.v. dose of Zn may be used to eliminate the need for venipuncture and the second Zn isotope. OBJECTIVES: To determine a constant (k) for the Zn enrichment of urine after i.v. administration of a dose of labeled Zn in Zn-replete subjects. To use 'k' to calculate fractional absorption of Zn, and to compare these values to values obtained using the standard dual isotope method. DESIGN: Single-arm cohort. SETTING: The Hospital for Sick Children, Toronto, Canada. SUBJECTS: Twenty-three healthy adults were recruited from the Metropolitan Toronto area. Seventeen subjects completed the study. INTERVENTIONS: A 2.29 mg i.v. dose of (67)Zn followed immediately by a 2.50 mg oral dose of (70)Zn. RESULTS: Population mean percentage enrichment (%E) of (67)Zn in urine was 1.43 (95% CI 1.26, 1.60). The ratio of the i.v. dose to mean %E in urine (k) was estimated to be 1.60 mg (95% CI 1.43, 1.82). There was no difference in the mean fractional absorption of Zn calculated using the single compared to the dual isotope method: 12.58% (95% CI 2.22, 22.94) vs 12.68% (95% CI 4.52, 20.85), respectively (P=0.89). The correlation coefficient between the two methods was 0.81 (P<0.0001). CONCLUSIONS: The dual isotope method may be replaced by using a constant (k) and a single oral dose of isotopic-enriched Zn to estimate fractional absorption of Zn within a population. SPONSORSHIP: Gerber Products Company, Fremont, MI.

Characteristics and outcomes of children with enterostomy feeding tubes: A study of 325 children.

OBJECTIVES: To examine the characteristics and outcomes of children with gastrostomy and gastrojejunostomy tubes inserted before age three years, and to identify the factors that predict removal of the enterostomy tubes within 12 months of insertion. DESIGN: Case review of a consecutive sample of 325 medical records. SETTING: A tertiary care paediatric hospital that is situated in a large metropolitan area. PATIENTS: All outpatients and inpatients from birth to 36 months of age who had an enterostomy tube inserted from 1994 to 1996. METHODS: No direct intervention was provided. In the subgroup of 203 patients with a follow-up period of at least 12 months after tube insertion, children whose tubes were removed within 12 months of insertion were compared with children who continued to receive tube feedings for 12 months or longer. RESULTS: At the time of tube insertion, the median age of patients was six months; 47% of the children for whom data were available were failing to thrive. Although 66 (21%) of 321 patients for whom data were available had their tubes removed, only 25 of the 203 (12%) patients with a follow-up period of 12 months or more had their tubes removed within 12 months of insertion. Children whose tubes were removed less than 12 months after insertion differed from children whose tubes were not removed with respect to medical diagnosis (no children with cerebral palsy had their tubes removed versus 33% of children with cancer who had their tube removed). Most children with failure to thrive at the time of tube insertion were also failing to thrive at the time of tube removal. CONCLUSION: Children with cerebral palsy are not likely to have enterostomy tubes removed within one year of insertion.

Developing and implementing food-based dietary guidance for fat in the diets of children.

This article discusses the process by which a country can effectively solve health problems through recommended changes in the nutrient content of the diet. Each country must consider not only the development of scientific guidelines suitable for its population, but also strategies for effective food-based dietary guidance to achieve the goal. This is best done by integrating health and dietary goals when forming scientific guidelines and by developing effective partnerships among the many sectors that influence the food supply and food selection. Using fat intake in children as an example, this article describes the determinants of success in achieving the goals of science-based dietary guidelines through food-based dietary guidance.

Discontinuation of enterostomy tube feeding by behavioral treatment in early childhood: a randomized controlled trial.

OBJECTIVE: To determine whether behavior therapy was more effective than nutritional therapy in obviating the need for enteral feeding in infants with resistance to feeding. STUDY DESIGN: Sixty-four children aged 4 to 36 months who were tube fed for at least 1 month and had resistance to feeding were randomly assigned to either behavioral or nutritional interventions (32 per group). For 7 consecutive weeks subjects and their primary feeders attended a weekly clinic with 1 of 2 dietitians followed by 4 follow-up visits. The nutritional intervention provided structured schedules and routines to stimulate the hunger/satiety cycle. The behavioral intervention provided the same schedules and routines plus behavioral therapy (extinction). The primary outcome measure was the proportion of successes, defined as infants no longer requiring tube feeding at the third follow-up visit in each group (4(1/2) months after start of trial). The decision to discontinue tube feeding was made by an independent observer who used criteria defined before the study commencement. RESULTS: Fifteen (47%) of 32 subjects in the behavioral group versus none in the nutritional group were successes (P <.001). CONCLUSION: Behavior therapy is more efficacious in eliminating the need for tube feeding than nutritional counseling alone.

Efficacy of meat and iron-fortified commercial cereal to prevent iron depletion in cow milk-fed infants 6 to 12 months of age: a randomized controlled trial.

OBJECTIVE: To determine whether utilization of iron from infant cereal and pureed meat was sufficient to prevent iron depletion and/or anaemia in infants 6 to 12 months old fed whole cow milk (WCM) as their primary milk source. DESIGN: Six-month-old infants were randomized into a treatment group (n = 43) receiving iron-fortified infant cereal (10.2 mg iron), pureed meat (0.75-1.7 mg iron) and WCM for six months or a control group (n = 54) receiving no dietary intervention. Haemoglobin < 110 g/L or ferritin < 10 micrograms/L (measured bi-monthly), confirmed in a second blood sample, defined end-points. RESULTS: Proportion reaching end-point was similar between the treatment (3/43) and control infants (5/54) (p = 0.66). Infants not complying with the protocol were at greater risk of reaching end-point (p = 0.0002). Change in haemoglobin and ferritin across age was similar in both groups. CONCLUSIONS: Iron deficiency is not a concern in WCM-fed infants after six months of age if iron-containing complementary foods are concurrently ingested.

Effects of amino acid dialysis compared to dextrose dialysis in children on continuous cycling peritoneal dialysis.

OBJECTIVE: To compare the biochemical and nutritional effects of amino acid dialysis with dextrose dialysis in children receiving continuous cycling peritoneal dialysis (CCPD). DESIGN: A prospective randomized cross-over study. SETTING: Nonhospitalized patients. PATIENTS: Seven children aged 1.8 to 16.0 years (mean 8.1 years) with end-stage renal disease who were receiving CCPD. INTERVENTIONS: Each patient received nighttime automated CCPD of dextrose, plus a single daytime dwell of either amino acid dialysate or dextrose dialysate. After 3 months, subjects crossed over to the alternative regimen for a subsequent 3 months. MAIN OUTCOME MEASURES: Creatinine clearance, ultrafiltration, urea, creatinine, electrolytes, total protein, albumin, fasting plasma amino acids, anthropometrics, total body nitrogen. RESULTS: Amino acid dialysis was comparable to dextrose dialysis for creatinine clearance and ultrafiltration. Plasma urea concentrations were higher during amino acid dialysis. No clinical side effects or worsening of metabolic acidosis was observed. Caloric intake increased and protein intake improved. Appetite and total body nitrogen increased in at least half the children during amino acid dialysis. Total plasma protein and albumin concentrations did not change significantly. Fasting plasma concentrations of amino acids after 3 months of amino acid dialysis were comparable to baseline values. For several amino acids, the dose-response curve was blunted after a single amino acid exchange following 3 months of amino acid dialysis, which may, in part, be due to the induction of hepatic enzyme synthesis. CONCLUSIONS: Amino acid dialysis is an efficient form of peritoneal dialysis that should be considered for children with poor nutritional status for whom enteral nutrition supplementation has been unsuccessful. Further study is needed to determine the optimal amount of amino acids to deliver, the best time to administer the amino acid dialysis fluid, and the benefits of adding dextrose to the amino acid solution.

Iron is well absorbed by healthy adults after ingestion of double-fortified (iron and dextran-coated iodine) table salt and urinary iodine excretion is unaffected.

Severe deficiencies of iron (Fe) and iodine (I) affect more than one third of the world's population. A table salt, fortified with I and Fe, would be useful in areas in which anemia and goiter coexist. However, interactions between the two minerals have prevented their simultaneous use as fortificants. A method has been developed to coat I with dextran such that after spraying onto table salt, Fe and I do not interact. Our objective was to determine the absorption of Fe and the urinary excretion of I from table salt when provided in meals designed to significantly inhibit or enhance Fe absorption. Subjects (n = 16) ingested Fe-enhancing and Fe-inhibiting meals containing 5 g of table salt with 0.39 micromol dextran-coated I as potassium iodide and 1 mg of Fe (ferrous fumarate labeled with 59Fe) per gram of salt. Subjects also received a reference dose of 3 mg of ferrous fumarate labeled with 59Fe to "correct" for interindividual variation in iron absorption at a later date. Measured by whole-body counting, Fe-absorption from the Fe-enhancing meal (36.2 +/- 12.0%, corrected; 13.5 +/- 13.8% uncorrected) was significantly higher than that from the Fe-inhibiting meal (7.4 +/- 11.3%, corrected; 4.0 +/- 8.4%, uncorrected) (P < 0.0001). Urinary excretion of iodine at baseline and postingestion were not significantly different (0.89 +/- 0.5 vs. 1.06 +/- 0.39 micromol/L, P < 0.47) and were within the normal range. We conclude that Fe was well absorbed but influenced by the composition of the meal and that urinary excretion of iodine was maintained in the normal range with dextran-coated iodine.

Disparity of serum transferrin receptor measurements among different assay methods.

OBJECTIVE: To highlight differences in the quantification of transferrin receptor (TfR) concentration (a reliable index of iron deficiency) between three different assay methods. DESIGN: Methods comparison of TfR measurements in 'elevated' and 'normal' human sera using the Ramco, Quantikine and 'Lab' assays. SETTING: The Hospital for Sick Children, Toronto, Ontario, Canada. SUBJECTS: Pooled TfR for elevated and normal human sera obtained from the Ramco TfR assay kit. MAIN OUTCOME MEASURES: Differences between TfR concentrations in normal and elevated samples and repeatability for each assay method and limits of agreement in TfR quantification between assay methods. RESULTS: The mean TfR concentrations for the elevated reference serum samples was higher than the normal reference samples within each individual assay (P < 0.001); however, measurement agreement between methods was poor. CONCLUSIONS: Recognition of the relative differences in the values obtained from each of the assays should affect the interpretation of TfR concentration as an index of iron deficiency.