Elizabeth Kimbrough Pradhan

Double blind, cluster randomised trial of low dose supplementation with vitamin A or β carotene on mortality related to pregnancy in Nepal

Abstract Objective: To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as βcarotene. Design: Double blind, cluster randomised, placebo controlled field trial. Setting: Rural southeast central plains of Nepal (Sarlahi district). Subjects: 44646 married women, of whom 20119 became pregnant 22189 times. Intervention: 270 wards randomised to 3groups of 90each for women to receive weekly a single oral supplement of placebo, vitamin A (7000¼g retinol equivalents) or βcarotene (42mg, or 7000¼g retinol equivalents) for over 31/2 years. Main outcome measures: All cause mortality in women during pregnancy up to 12weekspost partum (pregnancy related mortality) and mortality during pregnancy to 6weeks postpartum, excluding deaths apparently related to injury (maternal mortality). Results: Mortality related to pregnancy in the placebo, vitamin A, and βcarotene groups was 704,426,and 361deaths per 100000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60(0.37to 0.97) and 0.51(0.30to 0.86). This represented reductions of 40% (P<0.04)and 49% (P<0.01) among those who received vitamin A and βcarotene. Combined, vitaminA or βcarotene lowered mortality by 44% (0.56(0.37to 0.84), P<0.005) and reduced the maternal mortality ratio from 645to 385deaths per 100000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. Conclusion: Supplementation of women with either vitamin A or βcarotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.

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

Efficacy of vitamin A in reducing preschool child mortality in Nepal.

Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.

The epidemiology of ocular trauma in rural Nepal

Aims: To estimate the incidence of ocular injury in rural Nepal and identify details about these injuries that predict poor visual outcome. Methods: Reports of ocular trauma were collected from 1995 through 2000 from patients presenting to the only eye care clinic in Sarlahi district, Nepal. Patients were given a standard free eye examination and interviewed about the context of their injury. Follow up examination was performed 2–4 months after the initial injury. Results: 525 cases of incident ocular injury were reported, with a mean age of 28 years. Using census data, the incidence was 0.65 per 1000 males per year, and 0.38 per 1000 females per year. The most common types of injury were lacerating and blunt, with the majority occurring at home or in the fields. Upon presentation to the clinic, 26.4% of patients had a best corrected visual acuity worse than 20/60 in the injured eye, while 9.6% had visual acuity worse than 20/400. 82% were examined at follow up: 11.2% of patients had visual acuity worse than 20/60 and 4.6% had vision worse than 20/400. A poor visual outcome was associated with increased age, care sought at a site other than the eye clinic, and severe injury. 3% of patients were referred for further care at an eye hospital at the initial visit; 7% had sought additional care in the interim between visits, with this subset representing a more severe spectrum of injuries. Conclusions: The detrimental effects of delayed care or care outside of the specialty eye clinic may reflect geographic or economic barriers to care. For optimal visual outcomes, patients who are injured in a rural setting should recognise the injury and seek early care at a specialty eye care facility. Findings from our study suggest that trained non-ophthalmologists may be able to clinically manage many eye injuries encountered in a rural setting in the “developing” world, reducing the demand for acute services of ophthalmologists in remote locations of this highly agricultural country.

Risk factors for early infant mortality in Sarlahi district, Nepal.

OBJECTIVES Early infant mortality has not declined as rapidly as child mortality in many countries. Identification of risk factors for early infant mortality may help inform the design of intervention strategies. METHODS Over the period 1994-97, 15,469 live-born, singleton infants in rural Nepal were followed to 24 weeks of age to identify risk factors for mortality within 0-7 days, 8-28 days, and 4-24 weeks after the birth. FINDINGS In multivariate models, maternal and paternal education reduced mortality between 4 and 24 weeks only: odds ratios (OR) 0.28 (95% confidence interval (CI) = 0.12-0.66) and 0.63 (95% CI = 0.44-0.88), respectively. Miscarriage in the previous pregnancy predicted mortality in the first week of life (OR = 1.98, 95% CI = 1.37-2.87), whereas prior child deaths increased the risk of post-neonatal death (OR = 1.85, 95% CI 1.24-2.75). A larger maternal mid-upper arm circumference reduced the risk of infant death during the first week of life (OR = 0.88, 95% CI = 0.81-0.95). Infants of women who did not receive any tetanus vaccinations during pregnancy or who had severe illness during the third trimester were more likely to die in the neonatal period. Maternal mortality was strongly associated with infant mortality (OR = 6.43, 95% CI = 2.35-17.56 at 0-7 days; OR = 11.73, 95% CI = 3.82-36.00 at 8-28 days; and OR = 51.68, 95% CI = 20.26-131.80 at 4-24 weeks). CONCLUSION Risk factors for early infant mortality varied with the age of the infant. Factors amenable to intervention included efforts aimed at maternal morbidity and mortality and increased arm circumference during pregnancy.

Prevalence and risk factors for trachoma in Sarlahi district, Nepal.

AIMS: To estimate the prevalence of trachoma in preschool children in Sarlahi district, Nepal, and to identify risk factors for the disease. METHODS: A stratified random sample of 40 wards was selected for participation in a trachoma survey. Within each ward, a systematic 20% sample of children 24-76 months of age was chosen to determine the presence and severity of trachoma using the World Health Organisation grading system. RESULTS: A total of 891 children were selected and 836 (93.8%) were examined for trachoma from December 1990 to March 1991. The prevalence of active trachoma was 23.6% (21.9% follicular and 1.7% intense inflammatory). Cicatricial trachoma was not seen in this age group. The prevalence of trachoma ranged from 0 to 50% across wards with certain communities at much higher risk for trachoma than others. Three year old children had the highest prevalence of follicular (25.5%) and intense inflammatory trachoma (4.3%). Males and females had similar prevalence rates. Wards without any tube wells were at higher risk than those with one or more tube wells. Lower rates of trachoma were seen in families who lived in cement houses, had fewer people per room, more servants, more household goods, animals, and land. Hence, less access to water, crowding and lower socioeconomic status were risk factors for trachoma. CONCLUSIONS: Although follicular trachoma is prevalent, intense inflammatory trachoma is relatively rare and scarring was not observed in this preschool population. Hence, this population may not be at high risk for repeat infections leading to blindness in adulthood.

Child feeding and care behaviors are associated with xerophthalmia in rural Nepalese households

The study examined caregiver-child interactions, intrahousehold food allocation and general child care behaviors and their effect on childrens xerophthalmia status in the rural Terai region of Nepal. Seventy-eight households with a child having a history of xerophthalmia (cases) were matched with 78 households with a child of the same age having no history of xerophthalmia (controls). Seven day-long continuous monitoring observations were performed in each household (over 15 months) by trained Nepali observers, focusing on feeding and care of a focus child and his/her younger sibling. Nineteen different behavioral variables were operationalized, including serving method, second helpings, serving refusals, encouragement to eat, request intensity, meal serving order, food channeling, food sharing, positive social behaviors, negative social behaviors, and positive health behaviors. Automatic serving and request intensity were strongly negatively correlated, especially among younger siblings. Children who serve themselves receive less encouragement to eat. Those children who are refused in their requests for food tend to ask for food more frequently, for a longer time, and be less likely to self-serve. Children who eat from a shared plate are less likely to interact with a food server and more likely to self-serve. Negative social behavior towards children is associated with the child having to request food more frequently and a greater likelihood of being refused food. Children who receive positive health care from their caregivers are also more frequently asked if they would like food by the server and are encouraged to eat. Several caregiver child feeding behaviors were related to a childs risk of having past vitamin A deficiency. Controls were much more likely to be served food automatically. Cases were more likely to serve themselves food and have multiple servings of food. Cases were nearly two times more likely than controls to be treated with neglect or harshly, and much less likely than controls to have their health needs receive attention. Examining intrahousehold behavior is critical for understanding the causes of vitamin A deficiency in rural Nepalese children, and has great potential for identifying and improving interventions to improve childrens diets and care.

Risk of death following pregnancy in rural Nepal

OBJECTIVE To investigate the length of time following pregnancy during which the risk of mortality was elevated among women in rural Nepal. METHODS An analysis was performed of prospective data on women participating in the control group of a large, population-based trial. Weekly visits were made for three years to 14805 women aged 14-45 years. Pregnancy and vital status were assessed. A total of 7325 pregnancies were followed. Mortality during and following pregnancy, expressed on a person-time basis, was compared to referent mortality unrelated to pregnancy (52 weeks after pregnancy) in the same cohort. FINDINGS The relative risk (RR) of death during pregnancy but before the onset of labour was 0.93 (95% confidence interval (CI): 0.38-2.32). During the perinatal period, defined as lasting from the onset of labour until seven days after outcome, the RR of death was 37.02 (95% CI: 15.03-90.92). The RR for 2 to 6 weeks, 7 to 12 weeks, and 13 to 52 weeks after pregnancy were 4.82, 2.59 and 1.01 with 95% CI of 1.77-13.07, 0.81-8.26 and 0.40-2.53, respectively. The RR of death was 2.21 (95% CI. 1.03-4.71) during the conventional maternal mortality period (pregnancy until 6 weeks after outcome). It was 2.26 (95% CI: 1.05-4.90) when the period was extended to 12 weeks after pregnancy outcome. CONCLUSION The risk of mortality associated with pregnancy should be assessed over the first 12 weeks following outcome instead of over the first 6 weeks.

Data management for large community trials in Nepal.

The current accessibility and sophistication of hardware and software has made it possible to design high-quality data management systems for community-based trials in resource-poor environments. We designed, implemented, and operated an effective data management system for the Nepal Nutrition Intervention Project Sarlahi (NNIPS), a placebo-controlled community trial to assess the impact of vitamin A supplementation on the preschool mortality of 38,000 children in the Sarlahi district of Nepal. A data center was established in Kathmandu, approximately 8 hr drive from the study area. The trial is now completed and over 200,000 forms have been processed. The majority of potential data discrepancies were identified and corrected by field workers during the interviews. Supervisors and forms editors located at the field office corrected most data errors. Once forms reach Kathmandu, the average number of data entry errors was 3.1 per 10,000 keystrokes for the eight data entry operators employed during the study. Extensive computerized checking of data during data entry found out-of-range, missing, or inconsistent data in only 1% of forms. Timely analysis of field worker performance provided ongoing feedback to supervisors and analysis for the Data Safety and Monitoring Committee, and for publication of results.

Agreement Between Clinical Examination and Parental Morbidity Histories for Children in Nepal

Parental histories are often used to estimate the prevalence and the impact of interventions on child morbidity, but few studies have examined the agreement between parental histories and clinical examination. We compared clinical findings with a same-day parental morbidity history for pre-school-age children in rural Nepal. A 15 per cent sample of children from 40 wards in Sarlahi district, Nepal, was selected for participation and 814 same-day morbidity histories were obtained from parents. A clinician, masked to the parents history, visited the household 2-4 h later and examined the child for signs of morbidity symptoms about which the parent had previously been questioned. Signs included measurement of temperature, respiratory rate, examination of stools, ear discharge, and presence of persistent cough. Agreement between the history and clinical examination was excellent for ear infection (kappa = 0.75) and history of measles rash (kappa = 0.74), moderate to poor for diarrhoea (kappa = 0.21) and fever (kappa = 0.31), and there was no evidence of agreement for dysentery (kappa = -0.01), rapid breathing (kappa = 0.06), and cough (kappa = 0.09). The prevalence of dysentery, fever, cough, and rapid breathing was lower if clinical signs rather than histories were used. The prevalence of diarrhoea was higher if the presence of a loose stool in a cup rather than a history was used. The prevalence of ear infections and measles was comparable with both methods. The agreement between histories and clinical examination varies by morbidity type, as does the prevalence of morbidity estimated by one or other method.