Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial.

BACKGROUND: Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. METHODS AND FINDINGS: This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 µg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): -0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: -1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: -0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. CONCLUSIONS: In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

Erythrocyte DHA and AA in infancy is not associated with developmental status and cognitive functioning five years later in Nepalese children.

BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFA) especially docosahexaenoic acid (DHA) and arachidonic acid (AA) are crucial for normal brain development in utero and in early infancy. Data on fatty acid status and cognitive development in infants and children from low-income countries are scarce. METHODS: We examined the association between the DHA and AA status in infancy (n = 320) and developmental status and cognitive functioning five years later. At five years of age, we measured development by the Ages and Stages Questionnaire 3rd. ed. (ASQ-3) and cognitive functioning by subtests from the neuropsychological test battery NEPSY II. In addition, infant fatty acid composition in red blood cells (RBC) was analyzed. In multiple linear and logistic regression models, we estimated the associations between DHA and AA status in infancy and scores on the ASQ-3 and the NEPSY II subtests. RESULTS: There were no notable associations between infant AA and DHA status, and the scores on the ASQ-3 and the NEPSY II subtests five years later. It should be noted that we found better than expected concentrations of erythrocyte DHA and AA among the infants, and the ASQ scores were left-skewed, which limited the ability to identify associations. CONCLUSION: DHA and AA status in infancy is seemingly not related to neurodevelopment measured 5 years later in this peri-urban population from Nepal.

Maternal and infant vitamin B12 status during infancy predict linear growth at 5 years.

BACKGROUND: Many children worldwide have poor vitamin B12 status. The objective of this study was to estimate association between maternal and infant vitamin B12 status and long-term growth. METHODS: We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331). RESULTS: Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday. CONCLUSION: Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.

Erythrocyte fatty acid composition of Nepal breast-fed infants.

PURPOSE: Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk. METHODS: RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls. RESULTS: In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake. CONCLUSIONS: RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial.

BACKGROUND: Vitamin B12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B12 on the neurodevelopment and growth of young children in Nepal. METHODS/DESIGN: We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. DISCUSSION: If vitamin B12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.

Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children.

Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later.Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children. In regression models, we estimated the associations between vitamin B-12 status, including a combined indicator of vitamin B-12 status (3cB12) and scores on the ASQ-3 and NEPSY II subtests.Results: All markers of vitamin B-12 status with the exception of plasma cobalamin were significantly associated with the total ASQ-3 scores in the multiple regression models. A 1-unit increase in the 3cB12 score was associated with an increase in the total ASQ-3 score of 4.88 (95% CI: 2.09, 7.68; P = 0.001). Increases in both plasma tHcy and MMA (indicating poorer status) were associated with a decrease in scores on the NEPSY II affect recognition and geometric puzzle subtests. Each unit increment in 3cB12 scores was associated with increases of 0.82 (95% CI: 0.49, 1.14; P < 0.0005), 0.59 (95% CI: 0.10, 1.09; P = 0.020), and 0.24 (95% CI: 0.02, 0.47; P = 0.035) in the affect recognition, geometric puzzle, and block construction scores, respectively.Conclusions: Vitamin B-12 status in infancy is associated with development and performance on social perception tasks and visuospatial abilities at 5 y of age. The long-term effects of poor vitamin B-12 status in infancy need further investigation in randomized controlled trials.

25-Hydroxy-Vitamin D Concentration Is Not Affected by Severe or Non-Severe Pneumonia, or Inflammation, in Young Children.

Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2-35 months with severe (n = 43) and non-severe (n = 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14, 45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections.

Low Prevalence of Vitamin D Insufficiency among Nepalese Infants Despite High Prevalence of Vitamin D Insufficiency among Their Mothers.

BACKGROUND: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. OBJECTIVES: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. METHODS: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status. RESULTS: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability. CONCLUSION: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers.

Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal.

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135-377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (ß 3.0, 95% CI (0.2, 5.0)) and UIC (ß 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants.

Vitamin Status among Breastfed Infants in Bhaktapur, Nepal.

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B6, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5'-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B6 deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.

Low dietary diversity and micronutrient adequacy among lactating women in a peri-urban area of Nepal.

OBJECTIVE: The main objectives were to assess the adequacy of the micronutrient intakes of lactating women in a peri-urban area in Nepal and to describe the relationships between micronutrient intake adequacy, dietary diversity and sociodemographic variables. DESIGN: A cross-sectional survey was performed during 2008-2009. We used 24 h dietary recall to assess dietary intake on three non-consecutive days and calculated the probability of adequacy (PA) of the usual intake of eleven micronutrients and the overall mean probability of adequacy (MPA). A mean dietary diversity score (MDDS) was calculated of eight food groups averaged over 3 d. Multiple linear regression was used to identify the determinants of the MPA. SETTING: Bhaktapur municipality, Nepal. SUBJECTS: Lactating women (n 500), 17-44 years old, randomly selected. RESULTS: The mean usual energy intake was 8464 (sd 1305) kJ/d (2023 (sd 312) kcal/d), while the percentage of energy from protein, fat and carbohydrates was 11 %, 13 % and 76 %, respectively. The mean usual micronutrient intakes were below the estimated average requirements for all micronutrients, with the exception of vitamin C and Zn. The MPA across eleven micronutrients was 0·19 (sd 0·16). The diet was found to be monotonous (MDDS was 3·9 (sd 1·0)) and rice contributed to about 60 % of the energy intake. The multiple regression analyses showed that MPA was positively associated with energy intake, dietary diversity, women's educational level and socio-economic status, and was higher in the winter. CONCLUSIONS: The low micronutrient intakes are probably explained by low dietary diversity and a low intake of micronutrient-rich foods.

Iron deficiency is uncommon among lactating women in urban Nepal, despite a high risk of inadequate dietary iron intake.

The main objective of the present study was to examine the association between dietary Fe intake and dietary predictors of Fe status and Hb concentration among lactating women in Bhaktapur, Nepal. We included 500 randomly selected lactating women in a cross-sectional survey. Dietary information was obtained through three interactive 24 h recall interviews including personal recipes. Concentrations of Hb and plasma ferritin and soluble transferrin receptors were measured. The daily median Fe intake from food was 17·5 mg, and 70% of the women were found to be at the risk of inadequate dietary Fe intake. Approximately 90% of the women had taken Fe supplements in pregnancy. The prevalence of anaemia was 20% (Hb levels < 123 g/l) and that of Fe deficiency was 5% (plasma ferritin levels < 15 µg/l). In multiple regression analyses, there was a weak positive association between dietary Fe intake and body Fe (ß 0·03, 95% CI 0·014, 0·045). Among the women with children aged < 6 months, but not those with older infants, intake of Fe supplements in pregnancy for at least 6 months was positively associated with body Fe (P for interaction < 0·01). Due to a relatively high dietary intake of non-haem Fe combined with low bioavailability, a high proportion of the women in the present study were at the risk of inadequate intake of Fe. The low prevalence of anaemia and Fe deficiency may be explained by the majority of the women consuming Fe supplements in pregnancy.

Acute lower respiratory infection in childhood and household fuel use in Bhaktapur, Nepal.

BACKGROUND: Globally, solid fuels are used by about 3 billion people for cooking. These fuels have been associated with many health effects, including acute lower respiratory infection (ALRI) in young children. Nepal has a high prevalence of use of biomass for cooking and heating. OBJECTIVE: This case-control study was conducted among a population in the Bhaktapur municipality, Nepal, to investigate the relationship of cookfuel type to ALRI in young children. METHODS: Cases with ALRI and age-matched controls were enrolled from an open cohort of children 2-35 months old, under active monthly surveillance for ALRI. A questionnaire was used to obtain information on family characteristics, including household cooking and heating appliances and fuels. The main analysis was carried out using conditional logistic regression. Population-attributable fractions (PAF) for stove types were calculated. RESULTS: A total of 917 children (452 cases and 465 controls) were recruited into the study. Relative to use of electricity for cooking, ALRI was increased in association with any use of biomass stoves [odds ratio (OR) = 1.93; 95% CI: 1.24, 2.98], kerosene stoves (OR = 1.87; 95% CI: 1.24, 2.83), and gas stoves (OR = 1.62; 95% CI: 1.05, 2.50). Use of wood, kerosene, or coal heating was also associated with ALRI (OR = 1.45; 95% CI: 0.97, 2.14), compared with no heating or electricity or gas heating. PAFs for ALRI were 18.0% (95% CI: 8.1, 26.9%) and 18.7% (95% CI: 8.4%-27.8%), for biomass and kerosene stoves, respectively. CONCLUSIONS: The study supports previous reports indicating that use of biomass as a household fuel is a risk factor for ALRI, and provides new evidence that use of kerosene for cooking may also be a risk factor for ALRI in young children.

A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in young children.

BACKGROUND AND OBJECTIVE: Diarrhea and pneumonia are the leading causes of illness and death in children <5 years of age. Zinc supplementation is effective for treatment of acute diarrhea and can prevent pneumonia. In this trial, we measured the efficacy of zinc when given to children hospitalized and treated with antibiotics for severe pneumonia. METHODS: We enrolled 610 children aged 2 to 35 months who presented with severe pneumonia defined by the World Health Organization as cough and/or difficult breathing combined with lower chest indrawing. All children received standard antibiotic treatment and were randomized to receive zinc (10 mg in 2- to 11-month-olds and 20 mg in older children) or placebo daily for up to 14 days. The primary outcome was time to cessation of severe pneumonia. RESULTS: Zinc recipients recovered marginally faster, but this difference was not statistically significant (hazard ratio = 1.10, 95% CI 0.94-1.30). Similarly, the risk of treatment failure was slightly but not significantly lower in those who received zinc (risk ratio = 0.88 95% CI 0.71-1.10). CONCLUSIONS: Adjunct treatment with zinc reduced the time to cessation of severe pneumonia and the risk of treatment failure only marginally, if at all, in hospitalized children.

Infant feeding practices in Bhaktapur, Nepal: a cross-sectional, health facility based survey.

BACKGROUND: Promotion of proper breastfeeding practices for the first six months of life is the most cost-effective intervention for reducing childhood morbidity and mortality. However, the adherence to breastfeeding recommendations in many developing countries is not satisfactory. The aims of the study were to determine breastfeeding and infant feeding patterns at nine months of age and to assess factors influencing exclusive breastfeeding practices. METHODS: In Bhaktapur, Nepal, we carried out a cross-sectional survey of 325 infants who came for measles vaccination at the age of nine months. Mothers were interviewed on details regarding feeding of their child and health since birth. RESULTS: Three quarters of all mothers reported that they did not receive any information on breastfeeding during the antenatal visit. Two hundred and ninety five (91%) mothers gave colostrum and 185 (57%) initiated breastfeeding within one hour of delivery. The prevalence of exclusively breastfeeding at 1, 3 and 6 months were 240 (74%), 78 (24%) and 29 (9%), and partial feeding was initiated in 49 (15%), 124 (38%) and 257 (79%) babies, respectively. The main reason, according to the mother, for introducing other foods before six months of age was insufficient breast milk. In logistic regression analyses, mother's knowledge on how long child should be given only breast milk and not living in joint families were associated positively with exclusive or predominant breastfeeding for four months or beyond. CONCLUSIONS: Despite the high proportion of mothers who initiated breastfeeding immediately after birth, continuation of exclusive breastfeeding for up to six months was not common. Very few mothers received any information on breastfeeding during the antenatal visit, indicating a need for counseling on exclusive breastfeeding. Possible options for this counseling could be during antenatal visits and at regular clinic visits for vaccination.

RNA viruses in young Nepalese children hospitalized with severe pneumonia.

BACKGROUND: Pneumonia is among the leading causes of illness and death in children <5 years of age worldwide. There is little information on the viral etiology of severe pneumonia in low-income countries, where the disease burden is particularly high. METHODS: We analyzed nasopharyngeal aspirates from 629 children 2 to 35 months of age meeting World Health Organization criteria for severe pneumonia and presenting at Kanti Children's Hospital, Kathmandu, Nepal, from January 2006 through June 2008. We examined one specimen from each child for 7 respiratory viruses using reverse transcription polymerase chain reaction. RESULTS: We detected one or more respiratory viruses in 188 (30%; confidence interval: 26.4%-33.7%) of the 627 specimens with a valid polymerase chain reaction result, of which 88 (14%) yielded respiratory syncytial virus (RSV), 28 (4.5%) influenza A, 24 (5.8%) parainfluenza virus (PIV) type 3, 23 (3.7%) PIV type 1, 17 (2.7%) influenza B, 9 (1.4%) human metapneumovirus, and 5 (0.8%) PIV type 2. Episodes of severe pneumonia occurred in an epidemic pattern with 2 main annual peaks, the viral infections contributing importantly to these epidemics. The largest peaks of severe pneumonia coincided with peaks of RSV infection, which occurred during the last part of the monsoon season and in winter. CONCLUSIONS: RSV was the dominant respiratory viral pathogen detected in young Nepalese children hospitalized with severe pneumonia.

Two weeks of zinc administration to Nepalese children with pneumonia does not reduce the incidence of pneumonia or diarrhea during the next six months.

Diarrhea and pneumonia are the 2 main causes of death in children under 5 y of age. Short courses of zinc administration are now recommended for treatment of childhood diarrhea and some studies have also shown its beneficial effect on treatment of pneumonia. The objective of our study was to assess the efficacy of zinc administration (10 mg/d for children 2-11 mo and 20 mg/d for >or= 12 mo of age) for 14 d on preventing diarrheal and respiratory illnesses for 6 mo of follow-up. This was a randomized, double-blind, placebo-controlled trial in children 2-35 mo of age with community-acquired pneumonia. The number of illness episodes and time until the first episode of various illnesses were compared between the 2 study groups. After 14 d of zinc supplementation, plasma zinc was significantly higher in the group receiving zinc. However, this difference was not detectable at 1 and 2.5 mo after the end of zinc administration. Of 2628 enrolled cases, a total of 2599 (99%) were available for assessment after the completion of zinc supplementation. The number of hospital visits and the median number of days until the first episode of pneumonia, diarrhea, and dysentery was similar in the 2 groups. The hazard ratios (95% CI) were 1.02 (0.92, 1.14) for nonsevere pneumonia, 1.11 (0.72, 1.73) for severe pneumonia, 1.07 (0.91, 1.26) for diarrhea, and 0.96 (0.69, 1.34) for dysentery. A short course of zinc supplementation given during an episode of pneumonia did not prevent diarrheal or respiratory illness over the next 6 mo.

A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal.

BACKGROUND: Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed. OBJECTIVE: Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common. DESIGN: In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia. RESULTS: One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30). CONCLUSION: Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733.

Respiratory viruses in nepalese children with and without pneumonia: a case-control study.

BACKGROUND: The causative role of respiratory viruses detected in upper airway secretions in childhood pneumonia needs further investigation. OBJECTIVE: To measure the association between infection with respiratory RNA viruses and pneumonia in children. METHODS: From March 2006 to July 2007, we conducted a case-control study of 680 pneumonia cases (WHO criteria) and 680 randomly selected, concurrently sampled age-matched controls among children aged 2-35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each child was examined for 7 respiratory viruses using reverse transcription polymerase chain reaction. We calculated the matched odds ratios (MORs) for the detection of the individual viruses from a case compared with a control as measures of pathogenicity using conditional logistic regression. RESULTS: At least 1 virus was recovered in 248 (36.5%) cases and 48 (7.1%) controls. The MOR varied from 2.0 to 13.0; the highest associations were observed for parainfluenza virus type 3 (MOR 13.0; 95% confidence interval [CI] 6.0-28.0), respiratory syncytial virus (MOR 10.7; CI 4.6-24.6), and influenza A (MOR 6.3; CI 1.9-21.4). We observed that the association was lower for children age 2-5 months compared with older children for parainfluenza virus type 3 (P value for interaction 0.002). CONCLUSIONS: All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia.

Clinical presentation and severity of viral community-acquired pneumonia in young Nepalese children.

BACKGROUND: Most deaths from pneumonia in children <5 years of age occur in developing countries, where information about the clinical impact and severity of viral causes of respiratory infections is limited. METHODS: From June 29, 2004 to June 30, 2007 we evaluated 2230 cases of pneumonia (World Health Organization criteria) in children aged 2 to 35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each case was examined for 7 respiratory viruses using reverse-transcription polymerase chain reaction. We compared illness duration, severity, and treatment failure between cases positive and negative for the individual viruses in multiple regression models. RESULTS: A total of 2219 cases had a valid polymerase chain reaction result and were included in the analyses. Overall, 46.1% of cases were 2 to 11 months of age. Being infected with respiratory syncytial virus (RSV) was associated with lower chest indrawing (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.42-3.30) and, among infants, oxygen saturation <93% (OR: 1.88; CI: 1.32-2.69). Among the 2088 nonsevere pneumonia cases, those positive for RSV had a longer time to recovery (hazard ratio 0.82; CI 0.75-0.90; P < 0.001) and an increased risk of treatment failure (OR: 1.75; CI: 1.34-2.28; P < 0.001) than the RSV negative cases. CONCLUSIONS: Being infected with RSV was associated with a more severe clinical presentation of pneumonia, longer illness duration, and increased risk of treatment failure. The severity of RSV infection was age related, infants being more severely affected.