Risk factors for moderate acute malnutrition among children with acute diarrhoea in India and Tanzania: a secondary analysis of data from a randomized trial.

BACKGROUND: Moderate acute malnutrition (MAM) affects over 30 million children aged < 5 years worldwide. MAM may confer a greater risk of developing severe malnutrition and even mortality in children. Assessing risk factors for MAM may allow for earlier recognition of children at risk of deleterious health outcomes. OBJECTIVE: To determine risk factors associated with the prevalence and development of MAM among children aged 6 to 59 months with acute diarrhoea who received treatment with oral rehydration solution and zinc supplementation. METHODS: We conducted a secondary analysis of data from a randomized, dose-finding trial of zinc among children with acute diarrhoea in India and Tanzania. We used regression models to assess risk factors for prevalent MAM at the start of diarrhoea treatment and to identify risk factors associated with the development of MAM at 60 days. MAM was defined as weight for length (or height) Z score ≤-2 and > -3 or mid-upper arm circumference < 12.5 and ≥ 11.5 cm. RESULTS: A total of 4,500 children were enrolled; 593 (13.2%) had MAM at the baseline. MAM at baseline was significantly less common among children in Tanzania than in India (adjusted risk ratio [aRR] 0.37, 95% confidence interval [CI]: 0.30, 0.44, P < 0.001), in children aged 24- < 60 months versus 6- < 12 months (aRR 0.46, 95% CI: 0.38, 0.56, P < 0.001), and in families with household wealth index higher than the median (aRR 0.79, 95% CI: 0.68, 0.92, P = 0.002). Sixty days after outpatient treatment and follow-up, 87 (2.5%) children developed MAM. When compared to children aged 6- < 12 months, children aged 24- < 60 months had a 52% lower risk of developing MAM. Every one unit increase in weight for length (or height) Z score at enrolment was associated with a 93% lower risk of developing MAM during follow-up. CONCLUSIONS: Among children with diarrhoea, younger children and those from households with lower wealth were at greater risk of MAM. These children may benefit from targeted interventions focusing on feeding (targeted nutrition support for at-risk households) and follow up in order to reduce the occurrence of MAM and its consequences.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

Evaluating the efficacy of a multistrain probiotic supplementation for prevention of neonatal sepsis in 0-2-month-old low birth weight infants in India-the "ProSPoNS" Study protocol for a phase III, multicentric, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Progress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising. METHODS: A phase III, multicenter, randomized, double-blind, placebo-controlled study is being conducted at six sites in India. A total of 6144 healthy low birth weight (LBW) infants fulfilling the eligibility criteria would be enrolled within the first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex, and birth weight, would be done through an interactive web response system (IWRS) using a standard web browser and email service. Vivomixx®, a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1-ml/day dose for 30 days. The follow-up of enrolled infants for 60 days would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, and blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performing sepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. The study would be implemented as per the MRC guideline for the management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A contract research organization would be engaged for comprehensive monitoring and quality assurance. The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes of sepsis, possible serious bacterial infection (PSBI), and secondary outcomes. The codes will be broken after DMC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sites. DISCUSSION: This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high-risk group of low birth weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital-based studies, and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other low-middle-income countries. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197 . Registered on 16 May 2019.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania.

BACKGROUND: Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed. METHODS/DESIGN: The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6-59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration. DISCUSSION: The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6-59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea. TRIAL REGISTRATION NUMBER: NCT03078842. TRIAL STATUS: Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.

Efficacy of high zinc biofortified wheat in improvement of micronutrient status, and prevention of morbidity among preschool children and women - a double masked, randomized, controlled trial.

BACKGROUND: Biofortification of staple food crops with zinc (Zn) can be one of the cost-effective and sustainable strategies to combat zinc deficiency and prevent morbidity among the target population. Agronomic approaches such as application of Zn fertilizers to soil and/or foliar spray seem to be a practical tool for Zn biofortification of wheat. However, there is a need to evaluate its efficacy from randomized controlled trials. This study aimed to evaluate the efficacy of zinc biofortified wheat flour on zinc status and its impact on morbidity among children aged 4-6 years and non-pregnant non lactating woman of child bearing age (WCBA) in Delhi, India. METHODS: In a community based, double-masked randomized controlled trial, 6005 participants (WCBA and child pairs) were enrolled and randomly allocated to receive either high zinc biofortified wheat flour (HZn, 30 ppm zinc daily) or low zinc biofortified wheat flour (LZn, 20 ppm zinc daily) for 6 months (WCBA @ 360 g/day and children @ 120 g/day). Baseline and endline blood samples were obtained for assessing hematological markers; zinc status and data on compliance and morbidity were collected. RESULTS: Compliance rates were high; ~ 88% of the WCBAs in both the groups consumed 50% or more of recommended amount of biofortfied wheat flour during the follow up. Similarly 86.9% children in HZn and 87.5% in LZn consumed 50% or more of recommended wheat flour intake. There was no significant difference in mean zinc levels between the groups at end study. This observation might be due to a marginal difference in zinc content (10 ppm) between the HZn and LZn wheat flour, and a short intervention period. However a positive impact of bio-fortification on self-reported morbidity was observed. Compared to children in LZn group, children in HZn group had 17% (95% CI: 6 to 31%, p = 0.05) and 40% (95% CI: 16 to 57%; p = 0.0019) reduction in days with pneumonia and vomiting respectively. WCBA in the HZn group also showed a statistically significant 9% fewer days with fever compared to LZn group. CONCLUSIONS: Biofortified wheat flour had a good compliance among children and WCBAs. Significant improvement on some of the self-reported morbidity indicators suggests that evaluating longer-term effects of biofortification with higher grain zinc content would be more appropriate. TRIAL REGISTRATION: http://ctri.nic.in/Clinicaltrials/ , CTRI/2014/04/004527, Registered April 7, 2014.

Effect of 4 % chlorhexidine on cord colonization among hospital and community births in India: a randomized controlled study.

BACKGROUND: Infections are the single most important cause of neonatal mortality in developing countries. Results from trials in Asia evaluating the effect of chlorhexidine on neonatal mortality have been encouraging but limited data are available on the impact of cord cleansing on bacterial colonization. Further, no data from facility deliveries and impact with time is available. This pilot study was aimed to evaluate the impact of 4 % commercially prepared chlorhexidine on cord colonization and density of colonization among newborns in India. METHODS: Three hundred twenty-six newborns (hospital-247; community-79) were enrolled within 24 h of birth and randomly assigned to one of three groups: chlorhexidine, placebo or dry cord care. Umbilical swabs were collected at baseline, 2- and 48- hours after intervention application. RESULTS: At baseline, growth positivity (any bacterial growth) was 20 % (50 of 247 swabs) and 81 % (64 of 79 swabs) among hospital and community born neonates, respectively. In both settings, chlorhexidine compared to placebo and dry cord care, reduced colonization following 2- and 48-hour post application. Chlorhexidine significantly reduced 48-hour post application colony counts in comparison to placebo [Hospital: mean difference = -1.01; 95 % CI: -1.72, -0.30 Community: mean difference = -1.76; 95 % CI: -2.60, -0.93] and dry cord care [Hospital: mean difference = -1.16; 95 % CI: -1.93, -0.39 Community: mean difference = -2.23; 95 % CI: -3.18, -1.29]. Differences were similar for gram-positive and gram-negative bacteria. CONCLUSIONS: Cord cleansing with 4 % chlorhexidine soon after birth reduced colonization as well as density of colonization significantly; however this pilot study does not address the impact of chlorhexidine on mortality. The control preparation neither increased or decreased colonization. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01528852, Registered February 7, 2012.

Trial of improved practices approach to explore the acceptability and feasibility of different modes of chlorhexidine application for neonatal cord care in Pemba, Tanzania.

BACKGROUND: Infections are responsible for 30-40 % of 4 million neonatal deaths annually. Use of chlorhexidine (CHX), a broad-spectrum topical antiseptic with strong residual activity, for umbilical cord cleansing has been shown to reduce infections during the neonatal period. However, the challenge remains with regard to selection of best mode of CHX delivery. As a part of formative research, we undertook a qualitative study in Pemba Island as a pilot to explore the attitudes; beliefs and practices of the community and health workers related to delivery, newborn and cord care. During the second phase of formative research, we used Trials of Improved Practices (TIPs) methodology to explore the acceptance and impediments, for the three possible modes of chlorhexidine application- 100 ml bottle with cotton swab, 10 ml single use dropper bottle and 3 g single application squeeze tube containing gel, as an umbilical cord care intervention. METHODS: In this pilot study, 204 mother-newborn pairs were enrolled from hospital and community setting in Pemba, Tanzania using a randomized three period crossover design. Mothers/guardians, Trained Birth Attendants (TBA)/ medical staff and community health workers (CHWs) were requested to try three different modes of CHX application for cord cleaning. All participants were demonstrated the method of cord cleaning using all three modes of delivery; each delivery mode was used for 3 days and an interview was conducted on day 10 to collect summary of their experience. Acceptance and preference scores were calculated based on feedback from the participants. RESULTS: Of 204 mother-newborn pairs, 27 were lost to follow up. 177 mothers performed the intervention and applied CHX to the newborn cord for all 9 days. Mothers rated 10 ml dropper bottle (49.7 %) as most convenient in terms of ease and application. They selected 10 ml dropper bottle (44.6 %) as their first choice; gel tube (33.9 %) and 100 ml bottle (21.5 %) as their second and third choice. TBAs, medical staff and CHWs also preferred 10 ml dropper bottle (43.3 %) over 100 ml bottle (12.9 %) and gel (38.8 %). CONCLUSIONS: Overall acceptability of CHX application for cord cleansing was high. 10 ml single use dropper bottle was given highest preference for CHX application. An understanding of the attitudes, beliefs and cultural practices in the community and selection of the most acceptable mode of CHX delivery is essential to the design and implementation of the intervention trials examining the efficacy of CHX cord care in reducing neonatal mortality and subsequent implementation in the programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01528852 Registered February 3, 2012.

Compliance with home-based fortification strategies for delivery of iron and zinc: its effect on haematological and growth markers among 6-24 months old children in north India.

Compliance is a key component in successful implementation of the delivery of micronutrients among children. The present study evaluates the compliance with two home-based food fortification strategies (fortified complementary food or sprinkle) for providing iron and zinc among children aged 6-24 months. A total of 292 children were randomly allocated to receive either rice-based fortified complementary food and nutrition education (Cf = 101), sprinkle and nutrition education (Mp = 97), or nutrition education alone as control (Ed = 94). All the enrolled children were breastfed at the beginning of the study and were advised to continue breastfeeding. Biweekly information on compliance and anthropometry was collected. Complete haemogram estimation was conducted at baseline and end of the study. Compliance with the fortified complementary food was higher compared to sprinkle (Cf = 81%, Mp = 64% child-days). Consumption of the fortified complementary food for 6 months resulted in a significant increase in mean haemoglobin in the intervention group compared to control group (Cf 1.29 +/- 1.6 g/dL; Ed 0.23 +/- 1.3 g/dL; p < 0.001). Our results showed that fortified complementary food had higher compliance than sprinkle and is a suitable delivery mechanism for iron and zinc in preschool children.

Efficiency of red cell distribution width in identification of children aged 1-3 years with iron deficiency anemia against traditional hematological markers.

BACKGROUND: Current strategy to identify iron deficiency anemia relies on markers involving high costs. Reports have suggested red cell distribution width (RDW) as a potential screening test for identifying iron deficiency anemia (IDA) but studies in pediatric populations are lacking. Our study elucidates the discriminative ability of RDW for detecting IDA among young children. METHODS: 2091 blood reports of children aged 1-3 years from an urban low socio-economic population of Delhi were analyzed to evaluate the sensitivity of RDW in discriminating IDA using receiver's operating characteristic curve. Hemoglobin and RDW were estimated using coulter, zinc protoporphyrin with AVIV fluorometer and serum ferritin by enzyme linked immunosorbent assay. RESULTS: A total of 1026 samples were classified as iron deficient anemia using gold standard. As a marker of overall efficiency, area under the curve for RDW was 0.83 (95% CI, 0.81- 0.84; p < 0.001). Sensitivity of RDW at cut-off of 18% to detect iron deficiency anemia was 76.5% and specificity 73.1% yielding a positive predictive value of 73% and negative predictive value of 76%. At a cut-off of RDW 16.4%, the sensitivity was 94% and at a cut-off of 21%, the specificity was 95%. Combination of hemoglobin ≤ 10 g/dL and RDW >15%, yielded a sensitivity of 99% and specificity of 90%. These data suggest that simple coulter analysis estimating hemoglobin and RDW can be used for identification of children in need for iron therapy. CONCLUSIONS: In India and similar settings, RDW >15% with hemoglobin ≤ 10.0 g/dL identifies iron deficient anemic children without need for iron status markers which could help reduce cost of management especially in poor settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00255385.

Impact of micronutrient fortification of yoghurt on micronutrient status markers and growth - a randomized double blind controlled trial among school children in Bangladesh.

BACKGROUND: Interventions providing foods fortified with multiple micronutrients can be a cost-effective and sustainable strategy to improve micronutrient status and physical growth of school children. We evaluated the effect of micronutrient-fortified yoghurt on the biochemical status of important micronutrients (iron, zinc, iodine, vitamin A) as well as growth indicators among school children in Bogra district of Bangladesh. METHODS: In a double-masked randomized controlled trial (RCT) conducted in 4 primary schools, 1010 children from classes 1-4 (age 6-9 years) were randomly allocated to receive either micronutrient fortified yoghurt (FY, n = 501) or non-fortified yoghurt (NFY, n = 509). For one year, children were fed with 60 g yoghurt everyday providing 30% RDA for iron, zinc, iodine and vitamin A. Anthropometric measurements and blood/urine samples were collected at base-, mid- and end-line. All children (FY, n = 278, NFY, n = 293) consenting for the end-line blood sample were included in the present analyses. RESULTS: Both groups were comparable at baseline for socio-economic status variables, micronutrient status markers and anthropometry measures. Compliance was similar in both the groups. At baseline 53.4% of the population was anemic; 2.1% was iron deficient (ferritin <15.0 µg/L and TfR > 8.3 mg/L). Children in the FY group showed improvement in Hb (mean difference: 1.5; 95% CI: 0.4-2.5; p = 0.006) as compared to NFY group. Retinol binding protein (mean diff: 0.05; 95% CI: 0.002-0.09; p = 0.04) and iodine levels (mean difference: 39.87; 95% CI: 20.39-59.35; p < 0.001) decreased between base and end-line but the decrease was significantly less in the FY group. Compared to NFY, the FY group had better height gain velocity (mean diff: 0.32; 95% CI: 0.05-0.60; p = 0.02) and height-for-age z-scores (mean diff: 0.18; 95% CI: 0.02-0.33; p = 0.03). There was no difference in weight gain velocity, weight-for-age z-scores or Body Mass Index z-scores. CONCLUSION: In the absence of iron deficiency at baseline the impact on iron status would not be expected to be observed and hence cannot be evaluated. Improved Hb concentrations in the absence of a change in iron status suggest improved utilization of iron possibly due to vitamin A and zinc availability. Fortification improved height gain without affecting weight gain. TRIAL REGISTRATION: ClinicalTrial.gov: NCT00980733.

Prebiotic and probiotic fortified milk in prevention of morbidities among children: community-based, randomized, double-blind, controlled trial.

BACKGROUND: Recent reviews suggest common infectious diseases continue to be a major cause of death among preschool children in developing countries. Identification of feasible strategies to combat this disease burden is an important public health need. We evaluated the efficacy of adding prebiotic oligosaccharide and probiotic Bifidobacterium lactis HN019 to milk, in preventing diarrhea, respiratory infections and severe illnesses, in children aged 1-4 years as part of a four group study design, running two studies simultaneously. METHODS AND FINDINGS: In a community based double-masked, randomized controlled trial, children 1-3 years of age, willing to participate, were randomly allocated to receive either control milk (Co; n = 312) or the same milk fortified with 2.4 g/day of prebiotic oligosaccharide and 1.9x10(7) colony forming unit (c.f.u)/day of probiotic Bifidobacterium lactis HN019 (PP; n = 312). Children were followed up for 1 year providing data for 1-4 years. Biweekly household surveillance was conducted to gather information on compliance and morbidity. Both study groups were comparable at baseline; compliance to intervention was similar. Overall, there was no effect of prebiotic and probiotic on diarrhea (6% reduction, 95% Confidence Interval [CI]: -1 to 12%; p = 0.08). Incidence of dysentery episodes was reduced by 21% (95% CI: 0 to 38%; p = 0.05). Incidence of pneumonia was reduced by 24% (95% CI: 0 to 42%; p = 0.05) and severe acute lower respiratory infection (ALRI) by 35% (95% CI: 0 to 58%; p = 0.05). Compared to children in Co group, children in PP group had 16% (95% CI: 5 to 26%, p = 0.004) and 5% (95% CI: 0 to 10%; p = 0.05) reduction in days with severe illness and high fever respectively. CONCLUSIONS/SIGNIFICANCE: Milk can be a good medium for delivery of prebiotic and probiotic and resulted in significant reduction of dysentery, respiratory morbidity and febrile illness. Overall, impact of diarrhea was not significant. These findings need confirmation in other settings.

Micronutrient fortified milk improves iron status, anemia and growth among children 1-4 years: a double masked, randomized, controlled trial.

BACKGROUND: Multiple micronutrient deficiencies are highly prevalent among preschool children and often lead to anemia and growth faltering. Given the limited success of supplementation and health education programs, fortification of foods could be a viable and sustainable option. We report results from a community based double-masked, randomized trial among children 1-4 years evaluating the effects of micronutrients (especially of zinc and iron) delivered through fortified milk on growth, anemia and iron status markers as part of a four group study design, running two studies simultaneously. METHODS AND FINDINGS: Enrolled children (n = 633) were randomly allocated to receive either micronutrients fortified milk (MN = 316) or control milk (Co = 317). Intervention of MN milk provided additional 7.8 mg zinc, 9.6 mg iron, 4.2 microg selenium, 0.27 mg copper, 156 microg vitamin A, 40.2 mg vitamin C, and 7.5 mg vitamin E per day (three serves) for one year. Anthropometry was recorded at baseline, mid- and end-study. Hematological parameters were estimated at baseline and end-study. Both groups were comparable at baseline. Compliance was over 85% and did not vary between groups. Compared to children consuming Co milk, children consuming MN milk showed significant improvement in weight gain (difference of mean: 0.21 kg/year; 95% confidence interval [CI] 0.12 to 0.31, p<0.001) and height gain (difference of mean: 0.51 cm/year; 95% CI 0.27 to 0.75, p<0.001). Mean hemoglobin (Hb) (difference of 13.6 g/L; 95% CI 11.1 to 16.0, p<0.001) and serum ferritin levels (difference of 7.9 microg/L; 95% CI 5.4 to 10.5, p<0.001) also improved. Children in MN group had 88% (odds ratio = 0.12, 95% CI 0.08 to 0.20, p<0.001) lower risk of iron deficiency anemia. CONCLUSIONS/SIGNIFICANCE: Milk provides an acceptable and effective vehicle for delivery of specific micronutrients, especially zinc and iron. Micronutrient bundle improved growth and iron status and reduced anemia in children 1-4 years old.

Effects of Bifidobacterium lactis HN019 and prebiotic oligosaccharide added to milk on iron status, anemia, and growth among children 1 to 4 years old.

OBJECTIVE: To evaluate the effect of Bifidobacterium lactis HN019 and prebiotic-fortified milk on iron status, anemia, and growth among 1- to 4-year-old children. PATIENTS AND METHODS: In a community-based double-masked, controlled trial in a periurban population, 624 children were enrolled and randomly allocated to receive either milk fortified with additional probiotic and prebiotic (n = 312) or control milk (n = 312) for 1 year. Probiotic and prebiotic milk contained an additional 1.9 x 10 colony-forming units per day of probiotic B lactis HN019 and 2.4 g/day of prebiotic oligosaccharides milk. Hematological parameters were estimated at baseline and at the end of the study. Height and weight measurements were recorded at baseline, mid study, and the end of the study. Difference of means and multivariate regression models was used to examine the effect of intervention. RESULTS: Both study groups were similar at baseline. Compliance was high (>85%) and did not vary by intervention groups. As compared with non-fortified milk, consumption of probiotic- and prebiotic-fortified milk for a period of 1 year reduced the risk of being anemic and iron deficient by 45% (95% CI 11%, 66%; P = 0.01) and increased weight gain by 0.13 kg/year (95% CI 0.03, 0.23; P = 0.02). CONCLUSIONS: Preschoolers are usually fed milk, which has good acceptance and can be easily fortified for delivery of probiotics. Consumption of B lactis HN019 and prebiotic-fortified milk resulted in a smaller number of iron-deficient preschoolers and increased weight gain.

Zinc deficiency: descriptive epidemiology and morbidity among preschool children in peri-urban population in Delhi, India.

Community-based data relating to factors influencing zinc deficiency among preschool children in India are inadequate. Data of a large, double-blinded, randomized, controlled zinc-supplementation trial were used for assessing the descriptive epidemiology of zinc deficiency among children aged 6-35 months (n = 940). In total, 609 children were followed up for 120 days for information on morbidity. Of these children, 116 from the control group belonging to the upper and the lower 25th quartile of plasma zinc status at baseline were selected for assessing the association of zinc deficiency with prospective morbidity. At baseline, demographic, socioeconomic and dietary information was collected, and anthropometric measurements and levels of plasma zinc were assessed. At baseline, 73.3% of the children were zinc-deficient (plasma zinc < 70 microg/dL), of which 33.8% had levels of plasma zinc below 60 microg/dL. A significantly higher risk of morbidity was prevalent among the subjects with lower plasma zinc compared to those with higher levels of plasma zinc.

Validation of visual estimation of portion size consumed as a method for estimating food intake by young Indian children.

In this observational study, estimation of food intake was evaluated using recording of portion size consumed, instead of post-weighing, as a method. In total, 930 feeding episodes were observed among 128 children aged 12-24 months in which actual intake was available by pre- and post-weighing. For each offering and feeding episode, portion size consumed was recorded by an independent nutritionist-as none, less than half, half or more, and all. Using the pre-weighed offering, available intake was estimated by multiplying portion sizes by the estimated weight. The estimated mean intake was 510.4 kilojoules compared to actual intake of 510.7 kilojoules by weighing. Similar results were found with nestum (52.0 vs 56.2 g), bread (3.8 vs 3.7 g), puffed rice (1.7 vs 1.9 g), banana (31.3 vs 24.4 g), and milk (41.6 vs 44.2 mL). Recording portion size consumed and estimating food intake from that provides a good alternative to the time-consuming and often culturally-unacceptable method of post-weighing food each time after a feeding episode.

Effects of fortified milk on morbidity in young children in north India: community based, randomised, double masked placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of milk fortified with specific multiple micronutrients on morbidity in children compared with the same milk without fortification. DESIGN: Community based, double masked, individually randomised trial. SETTING: Peri-urban settlement in north India. PARTICIPANTS: Children (n=633) aged 1-3 randomly allocated to receive fortified milk (n=316) or control milk (n=317). INTERVENTION: One year of fortified milk providing additional 7.8 mg zinc, 9.6 mg iron, 4.2 microg selenium, 0.27 mg copper, 156 microg vitamin A, 40.2 mg vitamin C, 7.5 mg vitamin E per day (three feeds). MAIN OUTCOME MEASURES: Days with severe illnesses, incidence and prevalence of diarrhoea, and acute lower respiratory illness. RESULTS: Study groups were comparable at baseline; compliance in the groups was similar. Mean number of episodes of diarrhoea per child was 4.46 (SD 3.8) in the intervention (fortified milk) group and 5.36 (SD 4.1) in the control group. Mean number of episodes of acute lower respiratory illness was 0.62 (SD 1.1) and 0.83 (SD 1.4), respectively. The fortified milk reduced the odds for days with severe illnesses by 15% (95% confidence interval 5% to 24%), the incidence of diarrhoea by 18% (7% to 27%), and the incidence of acute lower respiratory illness by 26% (3% to 43%). Consistently greater beneficial effects were observed in children aged < or =24 months than in older children. CONCLUSION: Milk is well accepted as a means of delivery of micronutrients. Consumption of milk fortified with specific micronutrients can significantly reduce the burden of common morbidities among preschool children, especially in the first two years of life. TRIAL REGISTRATION: NCT00255385 [ClinicalTrials.gov].

Development and use of behavior and social interaction software installed on Palm handheld for observation of a child's social interactions with the environment.

In settings in developing countries, children often socialize with multiple socializing agents (peers, siblings, neighbors) apart from their parents, and thus, a measurement of a child's social interactions should be expanded beyond parental interactions. Since the environment plays a role in shaping a child's development, the measurement of child-socializing agents' interactions is important. We developed and used a computerized observational software Behavior and Social Interaction Software (BASIS) with a preloaded coding scheme installed on a handheld Palm device to record complex observations of interactions between children and socializing agents. Using BASIS, social interaction assessments were conducted on 573 preschool children for 1 h in their natural settings. Multiple screens with a set of choices in each screen were designed that included the child's location, broad activity, state, and interactions with child-socializing agents. Data were downloaded onto a computer and systematically analyzed. BASIS, installed on Palm OS (M-125), enabled the recording of the complex interactions of child-socializing agents that could not be recorded with manual forms. Thus, this tool provides an innovative and relatively accurate method for the systematic recording of social interactions in an unrestricted environment.