Percent of women with low serum vitamin A concentration
The percent of women ages 15 to 49 who were tested for serum vitamin A (retinol) and whose levels were found to be less than 0.70 umol/l for non-pregnant, non-lactating women and less than 1.05 umol/l for pregnant and lactating women. While the cut-off of 1.05 umol/l for pregnant and lactating
women is being used on a widespread basis, there is not yet international
consensus on this value, and the 0.70 umol/l is used as an alternative cut-off
(WHO, 2009). Levels below 0.35 umol/l represent severe vitamin A deficiency (VAD) in children and adults.
This indicator is calculated as:
(Number of women ages 15 to 49 with low serum vitamin A levels [<1.05 umol/l pregnant and lactating; <0.70umol/l non-pregnant, non-lactating] / Total number of women ages of 15 to 49 tested for serum vitamin A) x 100
Levels of retinol in serum on a population or subsample of women (note: plasma levels give comparable results, WHO, 1996). The gold standard for analysis of serum retinol levels is high-pressure liquid chromatography (HPLC). For more detail on serum retinol analysis including the use of dried blood spot samples see: Gorstein et al. (2007); Craft et al. (2000); Klemm et al. (2004).
Levels of serum retinol are affected by infections and subclinical inflammation. When possible, women’s reports on concurrent infections and fevers and/or blood serum measures of acute phase C-reactive protein are advised. Data can be disaggregated by age groups, parity, reproductive status (pregnant, lactating, and non-pregnant, non-lactating), trimester of pregnancy, level of severity of VAD, and where available, by relevant socioeconomic and demographic factors such as education, income, and urban/rural residence. Additionally, season of the year and land ownership have been found to influence vitamin A levels in some low-income populations through access to vitamin A and B-carotene rich foods (IVACG, 2004).
Population-based surveys (e.g., DHS and UNICEF-MICS); local and program-based studies
VAD contributes to maternal mortality, and other poor outcomes of pregnancy and lactation. It diminishes the body’s ability to fight infections and contributes to anemia. In its more severe forms, VAD can lead to night blindness in children and pregnant women and to blindness through progressive drying, ulceration, and necrosis of the cornea. Based on serum retinol levels from 406 surveys conducted between 1995 to 2005, WHO (2009) estimated 19.1 million pregnant women (15.3 percent) worldwide are at risk for VAD. The main underlying cause of VAD is a diet that is chronically insufficient in vitamin A and B-carotene that can lead to reduced body stores and fail to meet basic physiologic needs, such as, supporting tissue growth, normal metabolism, and resistance to infection.
Serum retinol has been the indicator used most often in making a biochemical assessment of vitamin A status. WHO has recommended that at least two biologic indicators (i.e., night blindness, biochemical, or histological) be used to determine if VAD exists as a public health problem, rather than relying on a single indicator (Gorstein, 2007). Serum retinol and night blindness during pregnancy are the most likely biological indicators to be collected in cross-sectional surveys, such as, DHS. This indicator relates to three of the Millennium Development Goals: #1. Reduce poverty and hunger; #4. Reduce child mortality; and #5. Improve maternal health.
Collecting blood samples is clearly essential for using this indicator. Because the ease of collecting blood samples varies by setting (e.g., it is particularly difficult in populations with high prevalence of HIV), the practicality of this indicator is limited.
Immunoassay of RBP is a lower-cost method compared with serum retinol HPLC and requires a fraction of the amount of serum volume. Immunoassays of RBP are being compared with serum retinol in dose response studies and in field settings where the methodology is showing promise as a surrogate measure to estimate VAD (PATH, 2005; Fujita at al., 2009). An alternative measure of vitamin A in lactating women is based on vitamin A concentration in breast milk. Breast milk retinol is very useful in evaluating vitamin interventions because it has been shown to be the biochemical indicator most sensitive to measuring the impact of increased vitamin A intakes and supplementation (Stoltzfus and Underwood, 1995). Breast milk retinol levels do not appear to be appreciably influenced by systemic inflammation (Dancheck et al., 2005). However, logistical difficulties in maintaining the sample under the necessary temperature conditions make it less feasible for use in the context of large scale population surveys.
Serum retinol concentrations normally are maintained within a narrow range in individuals with adequate stores of vitamin A in the liver. Thus, low serum retinol can be a useful indicator to identify people with low or depleted liver stores, but provides limited information when body stores of vitamin A are within normal ranges (WHO, 2009). In addition, transient decreases in serum retinol levels due to infections do not reflect changes in liver vitamin A stores and can interfere with use of serum retinol as an indicator. Because infections and other types of inflammation affect serum retinol levels, measurement of serum CRP or another acute phase protein is advised (Stephensen and Gildengorin, 2000). Hemodilution during pregnancy also affects serum retinol levels, which, in conjunction with increased acute phase proteins during pregnancy, also complicate interpretation. In spite of these limitations at the individual level, serum retinol can be informative for populations.
Simultaneous measurement of CRP is recommended to adjust serum retinol concentrations, particularly in populations with high prevalence of infections. Again, blood draws for CRP and laboratory costs become a limiting factor, and the assumptions underlying these adjustments can be problematic. Levels of CRP not only increase with age, but are increased during pregnancy (highest in third trimester) in addition to acute phase response to inflammation (Dijkhuizen, 2004). The process of determining serum retinol adjustments for elevated CRP values in adult women and setting cutoffs for elevated CRP and for VAD for pregnant women is complicated by the interactions of these factors.
nutrition, newborn (NB), adolescent, safe motherhood (SM)
Craft NE, Bulux J, Valdez C, Li Y, Solomons NW Retinol concentrations in capillary dried blood spots from healthy volunteers: method validation. American Journal of Clinical Nutrition (2000) 72(2):450-4.
Dancheck B, Nussenblatt V, Ricks MO, Kumwenda N, Neville MC, Moncrief DT, Taha TE, Semba RD. Breast milk retinol concentrations are not associated with systemic inflammation among breast-feeding women in Malawi, Journal of Nutrition. 2005 Feb;135(2): 223-6.
Dijkhuizen MA, Wieringa FT, and West CE, Pregnancy affects plasma concentration of retinol and acute phase proteins, Report of the XXII IVACG Meeting, Lima, Peru: November 2004.
Fujita M, Brindle E, Rocha A, Shell-Duncan B, Ndwema P, O’Connor KA, Assessment of the relative dose-response test on serum retinol-binding instead of serum retinol in determining low hepatic vitamin A stores, American Journal Clinical Nutrition, 2009:90:217:217-24.
Gorstein J, Sullivan KM, Parvanta I, Begin F. Indicators and Methods for Cross-Sectional Surveys of Vitamin and Mineral Status of Populations. The Micronutrient Initiative (Ottawa) and the Centers for Disease Control and Prevention (Atlanta), May 2007. http://www.who.int/vmnis/toolkit/mcn-micronutrient-surveys.pdf
IVACG, 2004, Vitamin A and the common agenda for micronutrients, Report of the XXII IVACG Meeting, Lima, Peru: Nov. 15-17.
Klemm RDW, Christian P, Craft NE, Khatry SK, West KP. Dried Blood Spot (DBS) Retinol Correlates with Serum Retinol and Detects a Response to Vitamin A in Pregnant Nepalese Women, Report of the XXII IVACG Meeting, Lima, Peru: November 2004.
PATH, Retinol binding protein enzyme immunoassay (RDP-EIA), Technology Solutions for Global Health, Nov. 2005.
Stephensen CB and Gildengorin G, Serum Retinol, the acute phase response, and the apparent misclassification of vitamin A status in the third National Health and Nutrition Examination Survey, American Journal Clinical Nutrition 2000;72:1170-8.
Stoltzfus RJ, Underwood BA, 1995, Breast-milk vitamin A as an indicator of the vitamin A status of women and infants, Bulletin of the World Health Organization, 5:703-711.
WHO, 1996, Indicators for Assessing Vitamin A Deficiency and their Application in Monitoring and Evaluating Intervention Programs, WHO Nutrition 96.10. Geneva.
WHO, 2009, Global prevalence of vitamin A deficiency in populations at risk 1995-2005: WHO database on vitamin A deficiency, Geneva: WHO.