Richard D. Semba

Maternal vitamin A deficiency and mother-to-child transmission of HIV-1

Studies show that around 10-40% HIV-positive women will give birth to children who are also infected. However, the risk factors for transmission from mother to child are not well understood and the effects of maternal nutritional status are unknown. We conducted a study of vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Serum vitamin A, height, weight, CD4 T-cell counts, and duration of breastfeeding were measured in 338 HIV-positive mothers whose infants HIV serostatus was known. Mother-to-child transmission of HIV was 21.9% among mothers whose infants survived to 12 months of age. Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants was lower than that in 264 mothers who did not transmit HIV to their infants (0.86 [0.03] vs 1.07 [0.02], p < 0.0001). We divided HIV positive mothers to 4 groups, those with vitamin A concentrations of less than 0.70, between 0.70 and 1.05, between 1.05 and 1.40, and greater than or equal to 1.40 mumol/L. The mother-to-child transmission rates for each group were 32.4%, 26.2%, 16.0%, and 7.2%, respectively (p < 0.0001). Maternal CD4 cell counts, CD4%, and CD4/CD8 ratio were also associated with increased mother-to-child transmission of HIV. Maternal age, body-mass index, and breastfeeding practices were not significantly associated with higher mother-to-child transmission. Our study suggests that maternal vitamin A deficiency contributes to mother-to-child transmission of HIV.

Human Immunodeficiency Virus Load in Breast Milk, Mastitis, and Mother-to-Child Transmission of Human Immunodeficiency Virus Type 1

Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.

Nonlinear Multisystem Physiological Dysregulation Associated With Frailty in Older Women: Implications for Etiology and Treatment

BACKGROUND Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear. METHODS Using data on women aged 70-79 years from the Womens Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures. RESULTS Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems. CONCLUSIONS Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty.

The anemia of vitamin A deficiency: epidemiology and pathogenesis

Objective: To gain insight into vitamin A deficiency as a cause of anemia.Methods: Comprehensive review of the scientific literature.Results: Although vitamin A deficiency is recognized to cause anemia, ‘vitamin A deficiency anemia’ lacks complete characterization as a distinct clinical entity. Vitamin A appears to be involved in the pathogenesis of anemia through diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection and reduction of the anemia of infection, and mobilization of iron stores from tissues. Epidemiological surveys show that the prevalence of anemia is high in populations affected by vitamin A deficiency in developing countries. Improvement of vitamin A status has generally been shown to reduce anemia, but the actual public health impact on anemia is unclear.Conclusions: Further work is needed to elucidate the biological mechanisms by which vitamin A causes anemia. The inclusion of anemia as an outcome measure in future micronutrient intervention studies should help provide further insight into the anemia of vitamin A deficiency.

Red Cell Distribution Width and Mortality in Older Adults: A Meta-analysis

BACKGROUND Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear. METHODS Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed. RESULTS Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11-1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12-1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07-1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07-1.18). Furthermore, the RDW-mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21-1.44). CONCLUSIONS RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.

Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype

BACKGROUND Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. METHODS We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids. RESULTS Humans are exposed to AGEs produced in the body, especially in individuals with abnormal glucose metabolism, and AGEs ingested in foods. AGEs cause widespread damage to tissues through upregulation of inflammation and cross-linking of collagen and other proteins. AGEs have been shown to adversely affect virtually all cells, tissues, and organ systems. Recent epidemiological studies demonstrate that elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals. CONCLUSIONS Based on these data, we propose that accumulation of AGEs accelerate the multisystem functional decline that occurs with aging, and therefore contribute to the aging phenotype. Exposure to AGEs can be reduced by restriction of dietary intake of AGEs and drug treatment with AGE inhibitors and AGE breakers. Modification of intake and circulating levels of AGEs may be a possible strategy to promote health in old age, especially because most Western foods are processed at high temperature and are rich in AGEs.

Micronutrients and the pathogenesis of human immunodeficiency virus infection

Micronutrient deficiencies may be common during human immunodeficiency virus (HIV) infection. Insufficient dietary intake, malabsorption, diarrhoea, and impaired storage and altered metabolism of micronutrients can contribute to the development of micronutrient deficiencies. Low plasma or serum levels of vitamins A, E, B6, B12 and C, carotenoids, Se, and Zn are common in many HIV-infected populations. Micronutrient deficiencies may contribute to the pathogenesis of HIV infection through increased oxidative stress and compromised immunity. Low levels or intakes of micronutrients such as vitamins A, E, B6 and B12, Zn and Se have been associated with adverse clinical outcomes during HIV infection, and new studies are emerging which suggest that micronutrient supplementation may help reduce morbidity and mortality during HIV infection.

Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial

BACKGROUND Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. METHODS This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P. falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. FINDINGS The number of P. falciparum febrile episodes (temperature > or = 37.5 degrees C with a parasite count of at least 8000/microL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p=0.0013). At the end of the study P. falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p=0.093 and p=0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p=0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p=0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124], p=0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. INTERPRETATION Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P. falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

Nutrition and health in developing countries

Nutrition and Development: A Historical Perspective. Maternal Mortality in Developing Countries. Low Birth Weight and Perinatal Mortality. Child Growth and Development. Diarrheal Diseases. Acute Lower-Respiratory Infections. Measles. Malaria. Tuberculosis. Human Immunodeficiency Virus Infection. Vitamin A Deficiency. Zinc Deficiency. Iron Deficiency and Anemia. Iodine Deficiency Disorders. Multiple Micronutrient Malnutrition: What Can Be Done? Malnutrition. The Nutrition Transition and Its Relationship to Demographic Change. The Emerging Problem of Obesity in Developing Countries. Rapid Urbanization and the Challenges of Obtaining Food and Nutrition Security. Assessing and Communicating Impact of Nutrition and Health Programs. The Economics of Nutritional Intervention. Research and Policy Directions. Index.

Effect of parental formal education on risk of child stunting in Indonesia and Bangladesh: a cross-sectional study

BACKGROUND Child stunting is associated with poor child development and increased mortality. Our aim was to determine the effect of length of maternal and paternal education on stunting in children under the age of 5 years. METHODS Data for indicators of child growth and of parental education and socioeconomic status were gathered from 590,570 families in Indonesia and 395,122 families in Bangladesh as part of major nutritional surveillance programmes. FINDINGS The prevalence of stunting in families in Indonesia was 33.2%, while that in Bangladesh was 50.7%. In Indonesia, greater maternal formal education led to a decrease of between 4.4% and 5% in the odds of child stunting (odds ratio per year 0.950, 95% CI 0.946-0.954 in rural settings; 0.956, 0.950-0.961 in urban settings); greater paternal formal education led to a decrease of 3% in the odds of child stunting (0.970, 0.967-0.974). In Bangladesh, greater maternal formal education led to a 4.6% decrease in the odds of child stunting (0.954, 0.951-0.957), while greater paternal formal education led to a decrease of between 2.9% and 5.4% in the odds of child stunting (0.971, 0.969-0.974 in rural settings; 0.946, 0.941-0.951 in urban settings). In Indonesia, high levels of maternal and paternal education were both associated with protective caregiving behaviours, including vitamin A capsule receipt, complete childhood immunisations, better sanitation, and use of iodised salt (all p<0.0001). INTERPRETATION Both maternal and paternal education are strong determinants of child stunting in families in Indonesia and Bangladesh.