K. P. West

IMPACT OF VITAMIN A SUPPLEMENTATION ON CHILDHOOD MORTALITY. A Randomised Controlled Community Trial

450 villages in northern Sumatra were randomly assigned to either participate in a vitamin A supplementation scheme (n = 229) or serve for 1 year as a control (n = 221). 25 939 preschool children were examined at baseline and again 11 to 13 months later. Capsules containing 200 000 IU vitamin A were distributed to preschool children aged over 1 year by local volunteers 1 to 3 months after baseline enumeration and again 6 months later. Among children aged 12-71 months at baseline, mortality in control villages (75/10 231, 7.3 per 1000) was 49% greater than in those where supplements were given (53/10 919, 4.9 per 1000) (p less than 0.05). The impact of vitamin A supplementation seemed to be greater in boys than in girls. These results support earlier observations linking mild vitamin A deficiency to increased mortality and suggest that supplements given to vitamin A deficient populations may decrease mortality by as much as 34%.

Abnormal T-cell subset proportions in vitamin-A-deficient children

Although vitamin A deficiency in children seems to increase susceptibility to infection and community trials have shown that vitamin A supplementation can reduce childhood mortality from infectious diseases, the underlying biological mechanisms are largely unknown. We conducted a randomised, double-masked, placebo-controlled clinical trial among children in West Java, Indonesia, to determine whether vitamin A deficiency is associated with abnormalities in T-cell subsets and whether vitamin A supplementation affects T-cell subsets. We studied 55 children aged 3-6 years--30 with xerophthalmia and 25 without. Acutely malnourished children (< 80% of reference weight-for-height) were excluded. CD4/CD8 ratios and the proportions of circulating CD4 naive, CD4 memory, CD8, CD45RA, and CD8, CD45RO T-cell subsets were measured. Children with xerophthalmia had lower CD4/CD8 ratios (p < 0.08), lower proportions of CD4 naive T cells (p < 0.03), and higher proportions of CD8, CD45RO T cells (p < 0.04) than those without xerophthalmia. 26 children were given vitamin A supplementation (60 mg retinol equivalent) and 29 received placebo. 5 weeks later the vitamin A group had higher CD4/CD8 ratios (p < 0.001), higher proportions of CD4 naive T cells (p < 0.01), and lower proportions of CD8, CD45RO T cells (p < 0.05) than the placebo group. Vitamin-A-deficient children have underlying immune abnormalities in T-cell subsets and these abnormalities are reversible with vitamin A supplementation.

Vitamin A deficiency and xerophthalmia among school-aged children in Southeastern Asia.

Objective: To determine provisional estimates of the extent of vitamin A (VA) deficiency and xerophthalmia among school-aged children.Design: Literature search of published, unpublished and website-based population survey and study reports, with country-specific imputation of prevalence rates and numbers of children affected by: (1) VA deficiency based on measured or imputed distributions of serum retinol concentration <0.70 μmol/l (equivalent to <20 μg/dl) and (2) xerophthalmia, by country.Setting: Countries within the WHO South-East Asian Region.Subjects: The target group for estimation was children 5–15 y of age.Interventions: None.Results: The estimated prevalence of VA deficiency is 23.4%, suggesting that there are ∼83 million VA-deficient school-aged children in the region, of whom 10.9% (9 million, at an overall prevalence of 2.6%) have mild xerophthalmia (night blindness or Bitots spot). Potentially blinding corneal xerophthalmia appears to be negligible at this age.Conclusions: VA deficiency, including mild xerophthalmia, appears to affect large numbers of school-aged children in South-East Asia. However, nationally representative data on the prevalence, risk factors and health consequences of VA deficiency among school-aged children are lacking within the region and globally, representing a future public health research priority.

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.

Supplementation with vitamin A early in life and subsequent risk of asthma

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006–2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989–1991). The second cohort was born to mothers who received vitamin A, &bgr;-carotene or placebo before, during and after pregnancy (1994–1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9–13 yrs and 6.6% in participants aged 14–23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p≥0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.

Circulating levels of retinol, tocopherol and carotenoid in Nepali pregnant and postpartum women following long-term β-carotene and vitamin A supplementation

Objective: To characterize circulating carotenoid and tocopherol levels in Nepali women during pregnancy and post-partum and to determine the effects of β-carotene and vitamin A supplementation on their concentration in serum.Design: Randomized community supplementation trial.Setting: The study was carried out from 1994 to 1997 in the Southern, rural plains District of Sarlahi, Nepal.Subjects: A total of 1431 married women had an ascertained pregnancy, of whom 1186 (83%) provided an analyzable serum sample during pregnancy; 1098 (77%) provided an analyzable 3–4 months post-partum serum sample.Interventions: Women received a weekly dose of vitamin A (7000 μg RE), β-carotene (42 mg) or placebo before, during and after pregnancy. Serum was analyzed for retinol, α-tocopherol, γ-tocopherol, β-carotene, α-carotene, lycopene, lutein+zeaxanthin, and β-cryptoxanthin concentrations during mid-pregnancy and at ∼3 months post-partum.Results: Compared to placebo, serum retinol, β-carotene, γ-tocopherol, β-cryptoxanthin and lutein+zeaxanthin concentrations were higher among β-carotene recipients during pregnancy and, except for β-cryptoxanthin, at postpartum. In the vitamin A group, serum retinol and β-cryptoxanthin were higher during pregnancy, and retinol and γ-tocopherol higher at postpartum. Lutein+zeaxanthin was the dominant carotenoid, regardless of treatment group, followed by serum β-carotene. Serum lycopene level was lowest, and very low compared to the US population. Serum retinol was higher, and carotenoid and α-tocopherol lower, at postpartum than during pregnancy in all groups.Conclusions: Pregnant and lactating Nepali women have lower serum carotenoid and tocopherol levels than well-nourished populations. β-carotene supplementation appeared to increase levels of tocopherol and other carotenoids in this population.Sponsorship: This study was carried out under Cooperative Agreement no DAN 0045-A-5094 and HRN A-00-97-00015-00 between the Office of Health and Nutrition, US Agency for International Development (USAID), Washington, DC and the Center for Human Nutrition, Johns Hopkins School of Public Health, Baltimore, MD, with additional support from Task Force Sight and Life, Basle, Switzerland, NIH grant no RR04060, and the Bill and Melinda Gates Foundation, Seattle, WA. The study was a joint undertaking between the Center for Human Nutrition and the National Society for the Prevention of Blindness, Kathmandu, Nepal.European Journal of Clinical Nutrition (2001) 55, 252–259

Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of β -carotene and vitamin A supplementation

Objective: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy.Design: Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or β-carotene supplementation on maternal mortality.Setting: Rural, southeastern plains of Nepal.Subjects and methods: A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy.Results: Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100 000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80–3.08). β-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11–0.89) and nonsmokers (RR=0.41, 95% CI: 0.19–0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was ∼30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality.Conclusions: Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. β-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers.

Infant feeding practices reflect antecedent risk of xerophthalmia in Nepali children.

Objective: To determine the relationship between infant feeding history and risk of xerophthalmia due to vitamin A deficiency (VAD) in early childhood. Design: A case-control study of previously xerophthalmic and non-xerophthalmic children. Setting: Rural lowland region of Nepal. Subjects: One hundred and fifty-six children (aged 1–6 y old), half of whom previously had xerophthalmia due to vitamin A-deficiency, the other half matched by locale, age and the presence and age of a younger sibling (n=102). Methods: Xerophthalmia was determined by trained ophthalmic assistants on the basis of current Bitot’s spots, corneal xerosis or report of night blindness. Infant feeding history was collected through a diet history method obtained from the mother of the focus child. Exploratory factor analysis was conducted to determine the presence of underlying patterns in infant feeding practices. Conditional logistic regression was used to estimate odds ratios. Results: Mothers of control children tended to have a higher level of education (P<0.10) and to have fewer children who had died (P<0.10) than mothers of case children. Feeding of meat (OR=0.09, CI=0.01–0.70) or fish (OR=0.41, CI=0.17–0.99) with liver, eggs (OR=0.11, CI=0.01–0.88) and mango (OR=0.28, CI=0.13–0.60) were protective in association with xerophthalmia in early childhood. Factor analysis uncovered several distinct patterns in infant feeding, which varied by age of the infant. Only the ‘animal flesh’ feeding pattern (factor), practiced in the second year of life, proved significantly protective from xerophthalmia (OR=0.43, CI=0.20–0.94). Feeding patterns of younger children closely paralleled those of their older siblings with and without VAD. Conclusions: The study supports the hypothesis that infant dietary practices can influence subsequent risk for VAD. Our findings emphasize the importance of introducing vitamin A-rich foods during weaning to reduce the risk of VAD-associated xerophthalmia in the later preschool years. Sponsorship: The project is funded through Cooperative Agreement No. DAN 0045-A-00-5094-00 between the Center for Human Nutrition/Dana Center for Preventive Ophthalmology, The Johns Hopkins University and The Office of Health and Nutrition, US Agency for International Development, with additional support from Task Force Sight and Life (Roche, Basel), and NIH shared instrument grant No. S10-RR 04060.

Seasonality in urinary and household salt iodine content among pregnant and lactating women of the plains of Nepal

Objective: To determine the extent and causes of iodine deficiency among women during pregnancy and lactation in the southeastern plains of Nepal.Design, Setting and Subjects: Urinary iodine (UI) was assessed as an indicator of iodine status in spot urine samples of women participating in a field trial in three rural communities in the plains of southeastern Nepal. Samples were collected during pregnancy (n=1021) and during lactation at 3–4 months postpartum (n=1028) at a central clinic; 613 women were assessed at both times. Salt iodine (SI) content was assessed semiquantitatively at 6–7 months postpartum in households (n=1572).Results: During pregnancy and lactation, median UI concentrations were 0.756 and 0.483 μmol/l, respectively, indicating mild iodine deficiency. UI and SI concentrations covaried markedly by season and were highest during hot, dry, premonsoon months and lowest during and following the humid monsoon season. Within women who contributed urine samples during both pregnancy and the postpartum period, iodine status determined by UI was not correlated. The percentage of households with adequately iodized salt (30 ppm) ranged from 85 to 44% from the hot, dry to the humid seasons, respectively.Conclusions: In the rural southern plains of Nepal, iodine deficiency remains a mild-to-moderate public health problem among pregnant and lactating women despite the availability of iodized salt. Marked seasonality in SI content may account for the lack of intraindividual correlation between maternal iodine status during pregnancy and postpartum periods and contribute to periodicity in the risk of iodine deficiency.Sponsorship: This study was funded by Cooperative Agreement HRN-A-00-97-00015-00 between Office of Nutrition, US Agency for International Development (USAID), Washington, DC, USA, and the Center for Human Nutrition (CHN), Department of International Health, the Bill and Melinda Gates Foundation, Seattle, WA, USA, and the Sight and Life Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Complex interactions with infection and diet may explain seasonal growth responses to vitamin A in preschool aged Indonesian children

Objective: To explore the potential contribution of respiratory infections and vitamin A intakes to the seasonal effect of vitamin A supplementation on child growth.Methods: Data from a randomized double-blind placebo-controlled trial, in which a single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6–48 months were used for the analysis. In total, 4430 child-treatment cycles were examined, and for each cycle the children had their dietary intake, weight, and height assessed at the start and end. Linear regression models of the difference in height and weight during each treatment cycle were used and the within-child correlation was adjusted using the generalized estimating equations (GEE). Other covariables in the model included age, sex, percentage of days with acute lower respiratory infection and diarrhea, and cumulative doses of vitamin A.Results: This study showed that a significant effect of vitamin A supplementation on linear growth was observed in all seasons in children with a low burden of respiratory infections, that is, <21.5% of days with respiratory illness. In each season, the highest effect was found in children with a low burden of respiratory infections and low vitamin A intakes, that is, intakes <400 RE/day. Children with a high burden of respiratory infections or high vitamin A intakes benefited less from vitamin A supplementation for their linear growth than children with a low burden of respiratory infections and low vitamin A intakes. Finally, there was no benefit for linear growth from vitamin A supplementation in children with both a high burden of respiratory infections and high vitamin A intakes regardless of the season.Conclusions: The effect of vitamin A supplementation on growth is dependent on season. Respiratory infections and vitamin A intakes are important factors underlying the seasonal effect of vitamin A supplementation on growth.