Inflammation throughout pregnancy and fetal growth restriction in rural Nepal.

Maternal systemic inflammation during pregnancy may restrict embryo-fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal-newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53-0.76) and 0.40 (0.33-0.50) g/l, and 0.56 (0.25-1.54) and 1.07 (0.43-2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10-6), and 0.45 (P = 3.1 × 10-5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10-7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.

Prevalence of Iron Deficiency and Anemia among Young Children with Acute Diarrhea in Bhaktapur, Nepal.

Iron deficiency anemia is still common in children under five years of age and may impair their growth and cognitive development. Diarrhea is the second most common reason for seeking medical care for young children in Nepal. However, neither screening programs nor effective preventive measures for anemia and iron deficiencies are in place among children with diarrhea in many developing countries. The aims of this study were to determine the prevalence of anemia and iron deficiency and explore their associations with clinical, socioeconomic, and anthropometric parameters in Nepalese children. This was a cross-sectional study based on 1232 children, six to 35 months old, with acute diarrhea participating in a zinc supplementation trial. The mean (SD) hemoglobin was 11.2 g/dL (1.2). Anemia was found in 493 children (40%); this estimate increased to 641 (52%) when we adjusted for the altitude of the study area (hemoglobin <11.3 g/dL). One in every three children had depleted iron stores and 198 (16%) of the children had both depleted iron stores and anemia, indicating iron deficiency anemia. The prevalence of anemia among children presenting with acute diarrhea was high but the degree of severity was mainly mild or moderate. Iron deficiency explained less than half of the total anemia, indicating other nutritional deficiencies inducing anemia might be common in this population.

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.

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.

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study.

BACKGROUND: Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries. METHODS: From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (rs = 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (rs = 0.55, P = 0.0005). CONCLUSION: Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.

Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial.

BACKGROUND: Neonatal mortality is the biggest contributor to global mortality of children younger than 5 years, and low birthweight is a crucial underlying factor. We tested the hypotheses that antenatal multiple micronutrient supplementation would increase infant birthweight and gestational duration. METHODS: We did a double-blind, randomised controlled trial in Dhanusha district, Nepal. Women attending for antenatal care with singleton pregnancies at up to 20 weeks' gestation were invited to participate. Participants were randomly allocated either routine iron and folic acid supplements (control; n=600) or a multiple micronutrient supplement providing a recommended daily allowance of 15 vitamins and minerals (intervention; n=600). Supplementation began at a minimum of 12 weeks' gestation and continued until delivery. Primary outcome measures were birthweight and gestational duration. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN88625934. FINDINGS: Birthweight was available for 523/600 infants in the control group and 529/600 in the intervention group. Mean birthweight was 2733 g (SD 422) in the control group and 2810 g (453) in the intervention group, representing a mean difference of 77 g (95% CI 24-130; p=0.004) and a relative fall in the proportion of low birthweight by 25%. No difference was recorded in the duration of gestation (0.2 weeks [-0.1 to 0.4]; p=0.12), infant length (0.3 cm [-0.1 to 0.6]; p=0.16), or head circumference (0.2 cm [-0.1 to 0.4]; p=0.18). INTERPRETATION: In a poor community in Nepal, consumption of a daily supplement containing a recommended daily allowance of 15 micronutrients in the second and third trimesters of pregnancy was associated with increased birthweight when compared with a standard iron and folic acid preparation. The effects on perinatal morbidity and mortality need further comparisons between studies. Published online March 3, 2005 http://image.thelancet.com/extras/04art11045web.pdf.

Current status of vitamin A deficiency and the National Vitamin A Control Program in Nepal: results of the 1998 National Micronutrient Status Survey.

The overall objective of the Nepal Micronutrient Status Survey (NMSS) was to assess the distribution and severity of micronutrient malnutrition, and to measure the progress achieved by different interventions. Data presented in this paper concern the prevalence of vitamin A deficiency (VAD) and the outreach and coverage of the National Vitamin A Supplementation activity. A multi-stage cluster sample design was employed that provided statistically representative data for each of thirteen eco-development strata (because of low population density, the West Mountains, Mid-west Mountains and Far-west Mountains were combined into a single stratum). The design allowed for aggregate estimates to be made at the national and ecological zone level. The survey showed a significant improvement in the status of clinical vitamin A deficiency in Nepal. The prevalence of both Bitot's spots and night-blindness among preschool children decreased from levels observed in surveys conducted in the previous twenty years. However, the prevalence of night-blindness was found to be 5% among women, and over 1% among school-aged children, which indicates that the entire population is vulnerable to VAD. These observations support findings from other surveys that have noted a high prevalence of maternal night-blindness in Nepal. Biochemical data collected as part of the survey indicated a high prevalence of low serum retinol (< 0.70 mumol/l), particularly among preschool children. Almost one of every three children (32.3%) and one of every six women (16.6%) had low serum retinol values. Low serum retinol among preschool children was associated with young age (6-11 months), rural location, wasting, presence of night-blindness and Bitot's spots, and residence in the Terai or Mountains. Similarly, sub-clinical VAD in women was associated with age (less than 20 years), pregnancy, the presence of night-blindness and residence in the Terai or Mountains. In the 42 districts covered by the National Vitamin A Programme (NVAP), more than 87% of preschool children were reached with vitamin A capsules. In addition to this, the National Immunisation Day (NID) provided oral polio vaccine drops to an estimated 95.7% of children 12-59 months. Awareness of the importance of vitamin A was, however, much higher in the NVAP districts than in non-programme districts. As would be expected, clinical VAD was most prevalent among children who had not received vitamin A during the most recent vitamin A capsule distribution. Indeed, the data show that vitamin A capsule receipt among children conferred a 59% protective effect for night-blindness and a 51% effect for Bitot's spots. These results point to significant progress having been achieved by the NVAP and NID capsule distribution activities.

Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial.

OBJECTIVE: To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women. DESIGN: Double blind cluster randomised controlled trial. SETTING: Rural community in south eastern Nepal. PARTICIPANTS: 4926 pregnant women and 4130 live born infants. INTERVENTIONS: 426 communities were randomised to five regimens in which pregnant women received daily supplements of folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrients all given with vitamin A, or vitamin A alone (control). MAIN OUTCOME MEASURES: Birth weight, length, and head and chest circumference assessed within 72 hours of birth. Low birth weight was defined <2500 g. RESULTS: Supplementation with maternal folic acid alone had no effect on birth size. Folic acid-iron increased mean birth weight by 37 g (95% confidence interval -16 g to 90 g) and reduced the percentage of low birthweight babies (<2500 g) from 43% to 34% (16%; relative risk=0.84, 0.72 to 0.99). Folic acid-iron-zinc had no effect on birth size compared with controls. Multiple micronutrient supplementation increased birth weight by 64 g (12 g to 115 g) and reduced the percentage of low birthweight babies by 14% (0.86, 0.74 to 0.99). None of the supplement combinations reduced the incidence of preterm births. Folic acid-iron and multiple micronutrients increased head and chest circumference of babies, but not length. CONCLUSIONS: Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight. Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk.