Ramesh Adhikari

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

Abstract 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. What is already known on this topic Deficiencies in micronutrients are common in women in developing countries and have been associated with low birth weight and preterm delivery What this study adds In rural Nepal maternal supplementation with folic acid-iron reduced the incidence of low birth weight by 16% A multiple micronutrient supplement of 14 micronutrients, including folic acid, iron, and zinc, reduced low birth weight by 14%, thus conferring no advantage over folic acid-iron

Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial

BACKGROUND Omphalitis contributes to neonatal morbidity and mortality in developing countries. Umbilical cord cleansing with antiseptics might reduce infection and mortality risk, but has not been rigorously investigated. METHODS In our community-based, cluster-randomised trial, 413 communities in Sarlahi, Nepal, were randomly assigned to one of three cord-care regimens. 4934 infants were assigned to 4.0% chlorhexidine, 5107 to cleansing with soap and water, and 5082 to dry cord care. In intervention clusters, the newborn cord was cleansed in the home on days 1-4, 6, 8, and 10. In all clusters, the cord was examined for signs of infection (pus, redness, or swelling) on these visits and in follow-up visits on days 12, 14, 21, and 28. Incidence of omphalitis was defined under three sign-based algorithms, with increasing severity. Infant vital status was recorded for 28 completed days. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. Analysis was by intention-to-treat. This trial is registered with , number NCT00109616. FINDINGS Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group. Severe omphalitis in chlorhexidine clusters was reduced by 75% (incidence rate ratio 0.25, 95% CI 0.12-0.53; 13 infections/4839 neonatal periods) compared with dry cord-care clusters (52/4930). Neonatal mortality was 24% lower in the chlorhexidine group (relative risk 0.76 [95% CI 0.55-1.04]) than in the dry cord care group. In infants enrolled within the first 24 h, mortality was significantly reduced by 34% in the chlorhexidine group (0.66 [0.46-0.95]). Soap and water did not reduce infection or mortality risk. INTERPRETATION Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality.

Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial

INTRODUCTION Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent. Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient populations, but little is known about the risks of mortality and morbidity associated with supplementation. METHODS We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-36 months and residing in southern Nepal. We randomly assigned children daily oral supplementation to age 36 months with: iron (12.5 mg) and folic acid (50 microg; n=8337), zinc alone (10 mg), iron, folic acid, and zinc (n=9230), or placebo (n=8683); children aged 1-11 months received half the dose. Our primary outcome measure was all-cause mortality, and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by intention to treat. This study is registered at , number NCT00109551. FINDINGS The iron and folic acid-containing groups of the study were stopped early in November, 2003, on the recommendation of the data and safety monitoring board; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed. We continued to enroll children to the placebo and zinc alone groups. 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up. There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo (HR 1.03, 95% CI 0.78-1.37, and 1.00, 0.74-1.34, respectively). There were no significant differences in the attack rates for diarrhoea, dysentery, or respiratory infections between groups, although all the relative risks except one indicated modest, non-significant protective effects. INTERPRETATION Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death, but might protect against diarrhoea, dysentery, and acute respiratory illness.

Impact of Newborn Skin-Cleansing With Chlorhexidine on Neonatal Mortality in Southern Nepal: A Community-Based, Cluster-Randomized Trial

OBJECTIVE. Hospital-based data from Africa suggest that newborn skin-cleansing with chlorhexidine may reduce neonatal mortality. Evaluation of this intervention in the communities where most births occur in the home has not been done. Our objective was to assess the efficacy of a 1-time skin-cleansing of newborn infants with 0.25% chlorhexidine on neonatal mortality. METHODS. The design was a community-based, placebo-controlled, cluster-randomized trial in Sarlahi District in southern Nepal. Newborn infants were cleansed with infant wipes that contained 0.25% chlorhexidine or placebo solution as soon as possible after delivery in the home (median: 5.8 hours). The primary outcome was all-cause mortality by 28 days. After the completion of the randomized phase, all newborns in study clusters were converted to chlorhexidine treatment for the subsequent 9 months. RESULTS. A total of 17530 live births occurred in the enrolled sectors, 8650 and 8880 in the chlorhexidine and placebo groups, respectively. Baseline characteristics were similar in the treatment groups. Intention-to-treat analysis among all live births showed no impact of the intervention on neonatal mortality. Among live-born infants who actually received their assigned treatment (98.7%), there was a nonsignificant 11% lower neonatal mortality rate among those who were treated with chlorhexidine compared with placebo. Low birth weight infants had a statistically significant 28% reduction in neonatal mortality; there was no significant difference among infants who were born weighing ≥2500 g. After conversion to active treatment in the placebo clusters, there was a 37% reduction in mortality among low birth weight infants in the placebo clusters versus no change in the chlorhexidine clusters. CONCLUSIONS. Newborn skin-wiping with chlorhexidine solution once, soon after birth, reduced neonatal mortality only among low birth weight infants. Evidence from additional trials is needed to determine whether this inexpensive and simple intervention could improve survival significantly among low birth weight infants in settings where home delivery is common and hygiene practices are poor.

Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial

BACKGROUND Zinc supplementation can reduce subsequent morbidity in children recovering from diarrhoea and respiratory illness in developing countries. However, whether routine supplementation would decrease morbidity and mortality in populations with zinc deficiency is unclear. We assessed the effect of daily zinc supplementation on children in southern Nepal. METHODS We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-35 months. Treatment groups were placebo, iron and folic acid, zinc, and iron and folic acid with zinc, with daily doses of 12.5 mg iron, 50 microg folic acid, and 10 mg zinc. Study staff gave children tablets on 2 days each week and left tablets with caregivers for other days. All children received vitamin A supplementation twice per year. Results of the iron arm of the trial have been reported previously. Between October, 2001, and January, 2006, 41,276 children were enrolled into the placebo (n=20,308) or zinc (n=20,968) groups and were followed-up for 60,636.3 person-years. The primary outcome was child mortality, and analyses were by intention to treat. Daily reports of signs and symptoms of common morbidities in stratified random subsamples of children were assessed every week for 12 months. This study is registered at ClinicalTrials.gov, number NCT00109551. FINDINGS 2505 children refused to continue the trial and 3219 children were lost to follow-up. There was no significant difference in mortality between the zinc and placebo groups (316 vs 333 deaths; hazard ratio 0.92, 95% CI 0.75-1.12). Zinc had no effect on mortality in children younger than 12 months (181 vs 168 deaths; 1.04, 0.83-1.31); mortality was lower, but not statistically significantly so, in older children receiving zinc (135 vs 165; 0.80, 0.60-1.06). The frequency and duration of diarrhoea, persistent diarrhoea, dysentery, and acute lower respiratory infections did not differ between the groups. INTERPRETATION Total mortality of children receiving zinc supplementation was not significantly different from that of children receiving placebo. Further data are needed from other populations with endemic zinc deficiency to confirm the potential age-specific effects reported in this study.

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.

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

BackgroundPneumonia 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.MethodsFrom 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.ResultsWe 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).ConclusionRespiratory 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.

Correlates of unintended pregnancy among currently pregnant married women in Nepal.

BackgroundWomen living in every country, irrespective of its development status, have been facing the problem of unintended pregnancy. Unintended pregnancy is an important public health issue in both developing and developed countries because of its negative association with the social and health outcomes for both mothers and children. This study aims to determine the prevalence and the factors influencing unintended pregnancy among currently pregnant married women in Nepal.MethodsThis paper reports on data drawn from Nepal Demographic and Health Survey (NDHS) which is a nationally representative survey. The analysis is restricted to currently pregnant married women at the time of survey. Association between unintended pregnancy and the explanatory variables was assessed in bivariate analysis using Chi-square tests. Logistic regression was used to assess the net effect of several independent variables on unintended pregnancy.ResultsMore than two-fifth of the currently pregnant women (41%) reported that their current pregnancy was unintended. The results indicate that age of women, age at first marriage, ideal number of children, religion, exposure to radio and knowledge of family planning methods were key predictors of unintended pregnancy. Experience of unintended pregnancy augments with womens age (odds ratio, 1.11). Similarly, increase in the womens age at first marriage reduces the likelihood of unintended pregnancy (odds ratio, 0.93). Those who were exposed to the radio were less likely (odds ratio, 0.63) to have unintended pregnancy compared to those who were not. Furthermore, those women who had higher level of knowledge about family planning methods were less likely to experience unintended pregnancy (odds ratio, 0.60) compared to those having lower level of knowledge.ConclusionOne of the important factors contributing to high level of maternal and infant mortality is unintended pregnancy. Programs should aim to reduce unintended pregnancy by focusing on all these identified factors so that infant and maternal mortality and morbidity as well as the need for abortion are decreased and the overall well-being of the family is maintained and enhanced.

Premarital Sexual Behavior among male college students of Kathmandu, Nepal

BackgroundIn Nepal, as in other Asian countries, the issue of sexuality still remains a taboo. Despite this fact, an increasing number of sexual activities is being reported by Nepalese students. This trend warrants serious and timely attention. Due to the sensitivity of the topic of premarital sexuality, youth receive inadequate education, guidance and services on reproductive health. The main objectives of this paper are to explore the sexual behavior especially focusing on prevalence of premarital sex among college men and to investigate the factors surrounding premarital sexual behavior.MethodsA cross-sectional survey of college students was conducted in April-May 2006. A self-administered questionnaire was completed by 573 male students. Association between premarital sex and the explanatory variables was assessed in bivariate analysis using Chi-square tests. The associations were further explored using multivariate logistic analysis.ResultsDespite the religious and cultural restrictions, about two-fifths of survey respondents (39%) reported that they have had premarital sex. The study has also shown that substantial proportions of students indulge in sexual activities as well as risky sexual behavior. Sex with commercial sex workers, multiple sex partners, and inconsistence use of condom with non-regular partner was common among the students. Less than two in five male students (57%) had used condom at the first sexual intercourse.The prevalence of premarital sex varied on different settings. Older students aged 20 and above were more likely to have premarital sex compared with younger students aged 15–19. Men who had liberal attitude towards male virginity at marriage were almost two times more likely to have engaged in premarital sex compared to their counterparts who have conservative attitude towards male virginity at marriage. Moreover, those students who believe in Hindu religion were more than two times (OR = 2.5) more likely to have premarital sex compared with those who follow other religions. Furthermore, those men who have close unmarried friends who have experienced premarital sexual intercourse were eight times (OR = 8.4) more likely to be sexually active compared to those who did not have such sexually active friends.ConclusionPrevalence of premarital sexual intercourse and risky sexual behavior are not uncommon in Nepal. Young people are exposed to health hazards due to their sexual behavior; hence sex education should be provided. School or college based sexuality education could benefit even out-of-school youths, because their partners often are students.

The effect of maternal micronutrient supplementation on early neonatal morbidity in rural Nepal: a randomised, controlled, community trial

Douthwaite, J., J. Moisan, C. Privezentzev, B. Soskic, S. Sabbah, S. Cohen, A. Collinson, E. England, C. Huntington, B. Kemp, L. Zhuang, S. Hudak, D. G. Rees, D. Goldberg, C. Barton, L. Chang, I. Vainshtein, M. Liang, L. Iciek, P. Ambery, M. Peakman, T. J. Vaughan, T. I. M. Tree, D. M. Sansom, M. A. Bowen, R. R. Minter, and L. Jermutus. 2017. A CD80-biased CTLA4-Ig fusion protein with superior in vivo efficacy by simultaneous engineering of affinity, selectivity, stability, and FcRn binding. J. Immunol., 198: 528–537.Objective: Micronutrient deficiencies during pregnancy may be linked to poor newborn health and poor host defences against infection. We assessed newborn morbidity to determine the effect of four combinations of antenatal micronutrient supplements. Design: Cluster-randomised, double-masked, controlled trial. Setting: Rural community in Nepal. Interventions: Women received daily supplements from early pregnancy through to 3 months postpartum of vitamin A alone (control) or vitamin A with folic acid, folic acid plus iron, folic acid plus iron plus zinc or a multiple micronutrient supplement containing these and 11 other nutrients. Main outcome measures: Infants were visited in their home at birth (n = 3927) and for each of 9 days thereafter to elicit a 24-h history of nine infant morbidity symptoms, measure infant respiratory rate and axial temperature, and assess the infant for chest indrawing. At 6 weeks of age, infants were visited again in their homes to elicit a 30-day and 7-day history of 10 morbidity symptoms using parental recall. Results: Maternal micronutrient supplementation had no effect on 10-day morbidity or morbidity 30-day and 7-day morbidity assessed at 6 weeks of age all relative risks were close to 1. Symptoms of birth asphyxia increased by about 60% (p<0.05) in infants of women who received the multiple micronutrient supplement compared with the control. Symptoms of combinations of sepsis, preterm and birth asphyxia were associated with 8- to 14-fold increased odds of 6-month infant mortality. Conclusions: None of the combinations of antenatal micronutrient supplements tested improved symptoms of neonatal morbidity in the first 10 days of life or at 6 weeks of age. Further research is needed to elucidate the association and mechanism of increased risk of birth asphyxia following maternal multiple micronutrient supplementation. Trial registration numbers: NCT00115271.