Biodigester Cookstove Interventions and Child Diarrhea in Semirural Nepal: A Causal Analysis of Daily Observations.

BACKGROUND: Hundreds of thousands of biodigesters have been constructed in Nepal. These household-level systems use human and animal waste to produce clean-burning biogas used for cooking, which can reduce household air pollution from woodburning cookstoves and prevent respiratory illnesses. The biodigesters, typically operated by female caregivers, require the handling of animal waste, which may increase domestic fecal contamination, exposure to diarrheal pathogens, and the risk of enteric infections, especially among young children. OBJECTIVE: We estimated the effect of daily reported biogas cookstove use on incident diarrhea among children <5y old in the Kavrepalanchok District of Nepal. Secondarily, we assessed effect measure modification and statistical interaction of individual- and household-level covariates (child sex, child age, birth order, exclusive breastfeeding, proof of vaccination, roof type, sanitation, drinking water treatment, food insecurity) as well as recent 14-d acute lower respiratory infection (ALRI) and season. METHODS: We analyzed 300,133 person-days for 539 children in an observational prospective cohort study to estimate the average effect of biogas stove use on incident diarrhea using cross-validated targeted maximum likelihood estimation (CV-TMLE). RESULTS: Households reported using biogas cookstoves in the past 3 d for 23% of observed person-days. The adjusted relative risk of diarrhea for children exposed to biogas cookstove use was 1.31 (95% confidence interval (CI): 1.00, 1.71) compared to unexposed children. The estimated effect of biogas stove use on diarrhea was stronger among breastfed children (2.09; 95% CI: 1.35, 3.25) than for nonbreastfed children and stronger during the dry season (2.03; 95% CI: 1.17, 3.53) than in the wet season. Among children exposed to biogas cookstove use, those with a recent ALRI had the highest mean risk of diarrhea, estimated at 4.53 events (95% CI: 1.03, 8.04) per 1,000 person-days. DISCUSSION: This analysis provides new evidence that child diarrhea may be an unintended health risk of biogas cookstove use. Additional studies are needed to identify exposure pathways of fecal pathogen contamination associated with biodigesters to improve the safety of these widely distributed public health interventions. https://doi.org/10.1289/EHP9468.

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.

Pre-earthquake national patterns of preschool child undernutrition and household food insecurity in Nepal in 2013 and 2014.

BACKGROUND AND OBJECTIVES: Preschool undernutrition remains a burden in Nepal. This paper reports results of surveys in 2013 and 2014, examining patterns of child nutritional status across the country, associations with household food insecurity and antecedent comparative national data for subsequent evaluations of nutritional status following the earthquake in Nepal in 2015. METHODS AND STUDY DESIGN: A multi-stage sample was drawn comprising 21 sites in 75 districts of the country, representing the mountains, hills and Terai zones, providing proportionate to zonal samples of 4286 and 4947 households and 5401 and 5474 preschool children in each year, respectively. Children 6 to 59 months of age were measured for weight and height, expressed as standardized z-scores for height-for-age (HAZ), weight-for-height (WHZ), and stunting and wasting (<-2 z for each). The household food insecurity access scale (HFIAS) was used to measure food security. RESULTS: Between 2013 and 2014, HAZ decreased from a mean (SD) of -1.46 (1.39) to -1.54 (1.33) z-scores, while the prevalence of stunting increased from 35.5% to 37.4% (p<0.05 for both), evident in the mountains and Terai but not hills. In both years, wasting was highest (~22%) in the Terai versus mountains or hills (~8%). More households were classified food secure in 2014 (73%) than 2013 (59%), evident in all zones. CONCLUSIONS: Two midyear surveys in Nepal revealed a stable nutritional situation among preschool children, reflecting a pause in the long-term decline in stunting noted in previous years. The same period saw a slight reduction in wasting and improved household food security.

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.

Cobalamin and folate status in 6 to 35 months old children presenting with acute diarrhea in Bhaktapur, Nepal.

BACKGROUND: Cobalamin and folate are essential micronutrients and are important in DNA and RNA synthesis, cell proliferation, growth, hematopoiesis, and cognitive function. However, data on cobalamin and folate status are lacking particularly from young children residing in low and middle income countries. OBJECTIVE: To measure cobalamin and folate status and identifies their predictors among 6 to 35 months old children presenting with acute diarrhea. DESIGN: This was a cross-sectional study in 823 children presenting with acute diarrhea. We measured plasma cobalamin, folate, methylmalonic acid and total homocysteine who sought treatment for acute diarrhea between June 1998 and August 2000. RESULTS: The mean (SD) plasma concentrations of cobalamin, folate, total homocysteine and methylmalonic acid were 206 (124) pmol/L, 55 (32) nmol/L, 11.4 (5.6) µmol/L and 0.79 (1.2) µmol/L, respectively. The prevalence of low plasma cobalamin (<150 pmol/L) was 41% but less than 2% (15) children had low folate concentration (<10 nmol/L). Plasma homocysteine and methylmalonic acid concentrations were negatively associated with cobalamin concentration but not associated with folate status. The prevalence of cobalamin deficiency was higher in breastfed than non-breastfed children (44% vs 24%; p = <0.001). The prevalence of hyperhomocysteinemia (>10 µmol/L) and elevated methylmalonic acid (>0.28 µmol/L) were 73% and 52%, respectively. In the regression analyses, the plasma cobalamin concentration was positively associated with age, and introduction of animal or formula milk. CONCLUSIONS: Our study indicated that poor cobalamin status was common particularly among breastfed children. Folate deficiency was virtually none existent. Possible consequences of cobalamin deficiency in young children need to be explored.

Risk factors for extended duration of acute diarrhea in young children.

OBJECTIVE AND BACKGROUND: We sought to identify predictors of extended duration of diarrhea in young children, which contributes substantially to the nearly 1 1/2 million annual diarrheal deaths globally. METHODS: We followed 6-35 month old Nepalese children enrolled in the placebo-arm of a randomized controlled trial with 391 episodes of acute diarrhea from the day they were diagnosed until cessation of the episode. Using multiple logistic regression analysis, we identified independent risk factors for having diarrhea for more than 7 days after diagnosis. RESULTS: Infants had a 17 (95% CI 3.5, 83)-fold and toddlers (12 to 23 month olds) a 9.9 (95% CI 2.1, 47)-fold higher odds of having such illness duration compared to the older children. Not being breastfed was associated with a 9.3 (95% CI 2.4, 35.7)-fold increase in the odds for this outcome. The odds also increased with increasing stool frequency. Furthermore, having diarrhea in the monsoon season also increased the risk of prolonged illness. CONCLUSION: We found that high stool frequency, not being breastfed, young age and acquiring diarrhea in the rainy season were risk factors for prolonged diarrhea. In populations such as ours, breastfeeding may be the most important modifiable risk factor for extended duration of diarrhea.

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.

Incidence of and risk factors for neonatal respiratory depression and encephalopathy in rural Sarlahi, Nepal.

OBJECTIVES: To characterize the incidence of, risk factors for, and neonatal morbidity and mortality associated with respiratory depression at birth and neonatal encephalopathy (NE) among term infants in a developing country. METHODS: Data were collected prospectively in 2002-2006 during a community-based trial that enrolled 23 662 newborns in rural Nepal and evaluated the impact of umbilical-cord and skin cleansing on neonatal morbidity and mortality rates. Respiratory depression at birth and NE were defined on the basis of symptoms from maternal reports and study-worker observations during home visits. RESULTS: Respiratory depression at birth was reported for 19.7% of live births, and 79% of cases involved term infants without congenital anomalies. Among newborns with probable intrapartum-related respiratory depression (N = 3465), 112 (3%) died before their first home visit (presumed severe NE), and 178 (5%) eventually developed symptoms of NE. Overall, 629 term infants developed NE (28.1 cases per 1000 live births); 2% of cases were associated with congenital anomalies, 25% with infections, and 28% with a potential intrapartum event. The incidence of intrapartum-related NE was 13.0 cases per 1000 live births; the neonatal case fatality rate was 46%. Infants with NE more frequently experienced birth complications and were male, of multiple gestation, or born to nulliparous mothers. CONCLUSIONS: In Sarlahi, the incidence of neonatal respiratory depression and NE, associated neonatal case fatality, and morbidity prevalence are high. Action is required to increase coverage of skilled obstetric/neonatal care in this setting and to evaluate long-term impairments.

Community-based stillbirth rates and risk factors in rural Sarlahi, Nepal.

OBJECTIVE: To assess stillbirth rates and antepartum risk factors in rural Nepal. METHODS: Data were collected prospectively during a cluster-randomized, community-based trial in Sarlahi, Nepal, from 2002 to 2006. Multivariate regression modeling was performed to calculate adjusted relative risk estimates. RESULTS: Among 24531 births, the stillbirth rate was 35.4 per 1000 births (term stillbirth rate 21.2 per 1000 births). Most births occurred at home without a skilled birth attendant. The majority (69%) of intrapartum maternal deaths resulted in stillbirth. The adjusted RR (aRR) of stillbirth was 2.74 among nulliparas and 1.47 among mothers with history of a child death. Mothers above the age of 30 years carried a 1.59-fold higher risk for stillbirth than mothers who were 20-24 years old. The stillbirth risk was lower among households where the father had any formal education (aRR 0.70). Land ownership (aRR 0.85) and Pahadi ethnicity (aRR 0.67; reference: Madhesi ethnicity) were associated with significantly lower risks of stillbirth. CONCLUSION: Stillbirth rates were high in rural Nepal, with the majority of stillbirths occurring at full-term gestation. Nulliparity, history of prior child loss, maternal age above 30 years, Madhesi ethnicity, and socioeconomic disadvantage were significant risk factors for stillbirth. Clinicaltrials.govNCT00 109616.

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.

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.

Zinc deficiency is common among healthy women of reproductive age in Bhaktapur, Nepal.

Zinc deficiency is a major public health problem in many developing countries. However, its prevalence is still unknown in most populations. Women of reproductive age in developing countries are highly vulnerable to nutritional deficiencies, including that of zinc. To estimate the prevalence of zinc deficiency and to identify important dietary sources of zinc, we undertook a cross-sectional survey in 500 nonpregnant Nepalese women and measured their plasma zinc concentrations. We also examined the associations between plasma zinc and dietary intake of zinc or phytate, iron status, plasma concentrations of C-reactive protein, albumin, and hemoglobin. Food intake was estimated by 2 24-h dietary recalls and 1 FFQ for each woman. The plasma zinc concentration was (mean +/- SD) 8.5 +/- 2.4 micromol/L and more than three-quarters of the women were zinc deficient. Dietary zinc intake did not predict plasma zinc concentration, whereas phytate intake was negatively and significantly associated with plasma zinc. The other variables that were associated with plasma zinc were plasma albumin and hemoglobin concentration. Rice contributed 50% to the total estimated daily zinc intake and wheat and meat each contributed 15%. Rice also contributed 68% to the daily intake of phytate. In conclusion, we found that zinc deficiency was common in women of reproductive age and that the foods contributing substantial amounts of zinc also contributed importantly to the intake of phytate.

Risk of mortality subsequent to umbilical cord infection among newborns of southern Nepal: cord infection and mortality.

BACKGROUND: Neonatal sepsis may stem from local umbilical cord infections. Signs of cord infection are common in low-resource settings, yet the risk of mortality subsequent to these signs has not been quantified in either developed or developing countries. We compared the risk of mortality between infants with and without signs of umbilical cord infection during a community-based trial of chlorhexidine interventions in southern Nepal. METHODS: Newborns were evaluated for signs of umbilical cord infection (pus, redness, swelling). A nested case-control approach was used to estimate the odds of mortality between infants with and without umbilical cord infection as defined by various levels of severity. For each death in the parent trial, 10 controls were selected, matched on sex, treatment group, and number of cord assessments. The main outcome measures were all-cause and sepsis-specific mortality. RESULTS: Among 23,246 assessed infants, there were 392 deaths. Odds of all-cause mortality were 46% (8-98%) higher among infants with redness extending onto the abdominal skin. A nonsignificant increased odds of mortality [odds ratio (OR): 2.31; 95% confidence interval (CI): 0.66-8.10] was observed among infants with severe redness and pus. Infections occurring after the third day of life were associated with subsequent risk of all-cause (OR: 3.11; 95% CI: 1.68-5.74) and sepsis-specific (OR: 4.63; 95% CI: 2.15-9.96) mortality. CONCLUSIONS: This study provides evidence that common local signs of cord infection are associated with increased risk of mortality. Where exposure of the umbilical cord to potentially invasive pathogens is high, interventions to increase hygienic care of the cord should be promoted and including hand washing, avoiding harmful topical applications, and topical cord antisepsis.

Verbal autopsy methods to ascertain birth asphyxia deaths in a community-based setting in southern Nepal.

OBJECTIVES: The goals of this study were to (1) develop an approach to ascertain birth asphyxia deaths by using verbal autopsy data from a community-based setting in Nepal, and (2) explore variations in birth asphyxia mortality fractions by using different birth asphyxia case definitions and hierarchical classifications. PATIENTS AND METHODS: Data were prospectively collected during a cluster-randomized, community-based trial of health interventions on neonatal mortality in Sarlahi, Nepal from 2002 to 2006. To assign cause of death, 4 computer-assigned, symptom-based asphyxia case definitions; Nepali physician classification; and our independent review of verbal autopsy open narratives were used. Various hierarchical classification approaches to assign cause of death were also explored. RESULTS: Birth asphyxia specific mortality ranged from 26% to 54%, depending on the computer case definition used. There was poor agreement between computer and physician classification of birth asphyxia. By comparing computer results, physician results, and our independent ascertainment of cause of death, we identified 246 cases of birth asphyxia (32% of neonatal deaths). Allowing for >1 cause of death, 30% and 42% of asphyxia cases also met criteria for prematurity and serious infection, respectively. When a hierarchy was used to assign a single cause of death, the birth asphyxia proportionate mortality was reduced to 12% when identification of deaths because of congenital anomalies, prematurity, and serious infections preceded birth asphyxia. CONCLUSIONS: The use of various verbal autopsy definitions and hierarchical approaches to assign cause of death may substantially affect estimates of birth asphyxia-specific mortality and analyses of risk factors. Verbal autopsy methods need to be standardized and validated to generate accurate global estimates to direct policy and resource allocation in low-middle-income countries.

Risk factors for neonatal mortality due to birth asphyxia in southern Nepal: a prospective, community-based cohort study.

OBJECTIVE: Our goal was to identify antepartum, intrapartum, and infant risk factors for birth asphyxia mortality in a rural, low-resource, population-based cohort in southern Nepal. PATIENTS AND METHODS: Data were collected prospectively during a cluster-randomized, community-based trial evaluating the impact of newborn skin and umbilical cord cleansing on neonatal mortality and morbidity in Sarlahi, Nepal. A total of 23662 newborn infants were enrolled between September 2002 and January 2006. Multivariable regression modeling was performed to determine adjusted relative risk estimates of birth asphyxia mortality for antepartum, intrapartum, and infant risk factors. RESULTS: Birth asphyxia deaths (9.7/1000.0 live births) accounted for 30% of neonatal mortality. Antepartum risk factors for birth asphyxia mortality included low paternal education, Madeshi ethnicity, and primiparity. Facility delivery; maternal fever; maternal swelling of the face, hands, or feet; and multiple births were significant intrapartum risk factors for birth asphyxia mortality. Premature infants (<37 weeks) were at higher risk, and the combination of maternal fever and prematurity resulted in a 7-fold elevation in risk for birth asphyxia mortality compared to term infants of afebrile mothers. CONCLUSIONS: Maternal infections, prematurity, and multiple births are important risk factors for birth asphyxia mortality in the low-resource, community-based setting. Low socioeconomic status is highly associated with birth asphyxia, and the mechanisms leading to mortality need to be elucidated. The interaction between maternal infections and prematurity may be an important target for future community-based interventions to reduce the global impact of birth asphyxia on neonatal mortality.

A randomized controlled trial of the impact of chlorhexidine skin cleansing on bacterial colonization of hospital-born infants in Nepal.

BACKGROUND: Chlorhexidine skin cleansing might substantially reduce neonatal infection and mortality in developing countries. Few data exist on the impact of chlorhexidine cleansing on skin colonization of infants during the first day of life or on the absorption potential of chlorhexidine during newborn skin cleansing. METHODS: Hospital-born newborns in Kathmandu, Nepal were randomly allocated to full-body skin cleansing with 0.25%, 0.50%, or 1.00% chlorhexidine solution. Skin swabs were collected from the axilla, inguinal, and peri-umbilical areas before cleansing (baseline), and at 2 and 24 hours after treatment. Skin flora was quantified and organisms identified. In a subsample, heel prick blood was collected 24 hours after the cleansing and percutaneous absorption of chlorhexidine was assessed. RESULTS: Among 286 enrolled newborns, no adverse effects on skin were reported and body temperature was minimally reduced (mean reduction, 0.33 degrees C). In all groups, positive skin culture rates were significantly reduced at 2 hours but generally not at 24 hours; greater reductions were observed with higher concentrations of chlorhexidine. Effect at 24 hours was highest in the 1.00% group (37% lower positive skin culture rate). For 15 of 75 infants with heel pricks, chlorhexidine was detected at trace concentrations (<8 ng/mL, n = 14; 25.8 ng/mL, n = 1). CONCLUSIONS: Chlorhexidine skin cleansing seemed safe and reduced skin flora in newborns in a dose-dependent manner 2 hours after treatment. Greater residual effect at the highest concentration (1%) might provide broader benefit and may simplify combined maternal and neonatal regimens by matching the concentration used for vaginal cleansing during labor.

Risk factors for umbilical cord infection among newborns of southern Nepal.

Although umbilical cord infection contributes to neonatal mortality and morbidity and risk can be reduced with topical chlorhexidine, behavioral or other factors associated with cord infection in low-resource settings have not been examined. Data on potential risk factors for omphalitis were collected during a community-based, umbilical cord care trial in Nepal during 2002-2005. Newborns were evaluated in the home for signs of umbilical cord infection (pus, redness, and swelling). Omphalitis was defined as either pus discharge with erythema of the abdominal skin or severe redness (>2 cm extension from the cord stump) with or without pus. Multivariable regression modeling was used to examine associations between omphalitis and maternal, newborn, and household variables. Omphalitis was identified in 954 of 17,198 newborns (5.5%). Infection risk was 29% and 62% higher in infants receiving topical cord applications of mustard oil and other potentially unclean substances, respectively. Skin-to-skin contact (relative risk (RR) = 0.64, 95% confidence interval (CI): 0.43, 0.95) and hand washing by birth attendants (RR = 0.73, 95% CI: 0.64, 0.84) and caretakers (RR = 0.76, 95% CI: 0.60, 0.95) were associated with fewer infections. In this community, unhygienic newborn-care practices lead to continued high risk for omphalitis. In addition to topical antiseptics, simple, low-cost interventions such as hand washing, skin-to-skin contact, and avoiding unclean cord applications should be promoted by community-based health workers.