The acute and chronic toxic effects of vitamin A

This review which was prepared as part of the background documentation for a WHO expert consultation1 evaluates the nutrient adequacy of exclusive breastfeeding for term infants during the first 6 months of life. Nutrient intakes provided by human milk are compared with infant nutrient requirements. To avoid circular arguments biochemical and physiological methods independent of human milk are used to define these requirements. The review focuses on human-milk nutrients which may become growth limiting and on nutrients for which there is a high prevalence of maternal dietary deficiency in some parts of the world; it assesses the adequacy of energy protein calcium iron zinc and vitamins A B6 and D. This task is confounded by the fact that the physiological needs for vitamins A and D iron zinc – and possibly other nutrients – are met by the combined availability of nutrients in human milk and endogenous nutrient stores. (excerpt)

Nutrient Adequacy of Exclusive Breastfeeding for the Term Infant During the First Six Months of Life

Vitamin A supplementation to preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are likely to be the result of the actions of vitamin A on immunity. Some of the immunomodulatory mechanisms of vitamin A have been described in clinical trials and can be correlated with clinical outcomes of supplementation. The effects on morbidity from measles are related to enhanced antibody production and lymphocyte proliferation. Benefits for severe diarrhea could be attributable to the functions of vitamin A in sustaining the integrity of mucosal epithelia in the gut, whereas positive effects among HIV-infected children could also be related to increased T-cell lymphopoiesis. There is no conclusive evidence for a direct effect of vitamin A supplementation on cytokine production or lymphocyte activation. Under certain circumstances, vitamin A supplementation to infants has the potential to improve the antibody response to some vaccines, including tetanus and diphtheria toxoids and measles. There is limited research on the effects of vitamin A supplementation to adults and the elderly on their immune function; currently available data provide no consistent evidence for beneficial effects. Additional studies with these age groups are needed.

Effects of Vitamin A Supplementation on Immune Responses and Correlation with Clinical Outcomes

Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial.

Background
The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin Ad eficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.
Objectives
To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30March 2015) and reference lists of retrieved studies.
Selection criteria
All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
Main results
We reviewed 106 reports of 35 trials, published between 1931 and 2015. We included 19 trials including over 310,000 women,
excluded 15 trials and one is ongoing. Overall, seven trials were judged to be of low risk of bias, three were high risk of bias and for nine it was unclear.

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Vitamin A supplementation during pregnancy for maternal and newborn outcomes

Objectives: To evaluate the effect of vitamin A supplementation 24 h after delivery on breastmilk retinol concentration. Methods: Fifty low income women were randomly assigned to a single oral dose of 209 μmol of Vitamin A or none at delivery. Maternal serum and breastmilk retinol levels and infant morbidity and anthropometry were serially assessed. Results: Mean (95% CI) serum retinol levels increased in the supplemented mothers at 2.77 (2.3, 3.2) compared to 1.15 (0.9, 1.4) μmol/l in controls (P<0.05) and remained at a significantly higher level of 1.59 (1.4, 1.8) μmul/l compared to 1.33 (1.8, 1.5) μmol/l in the control group (P<0.001) up to a period of three months. Breastmilk retinol concentration was also greater at 24 h after supplementation, mean (CI) 11.34 (9.0, 13.7) μmol/l, compared to 2.95 (2.3, 3.6) μmol/l in the control group (P<0.0001), and remained higher for the next six months at 1.06 (0.9, ,1.3) μmol/l compared to 0.73 (0.6, 0.8) μmol/l in the control group (P<0.02). Infants of the supplemented mothers had reduced mean duration of respiratory tract infection of 3.1 (2.7, 3.5) days compared to 3.7 (3.3, 4.2) days (P<0.03) and mean incidence of febrile illness 0.1 (0.1, 0.1) compared to control infants 0.3 (0.3, 0.3) days, (P<0.002). Conclusion: Vitamin A supplementation of malnourished mothers maintains higher breastmilk retinol concentration for at least six months and reduces the duration of respiratory tract infection and febrile illness in their breastfed infants. Sponsorship: The study was supported by the International Centre for Diarrhoeal Disease Research and the United States Agency for International Development.

SM Akramuzzaman

Papers

Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants