Key messages
• The two most common tests (serum or plasma retinol and retinol-binding protein) cannot reliably identify at-risk individuals with or without vitamin A deficiency in the community or clinics.

• This may mean that using these tests could lead to over- or underestimated levels of low vitamin A at the population level and incorrect diagnosis of individuals.

• Estimates of test accuracy should improve as more studies become available.

Why is it important to improve screening for vitamin A?
Vitamin A, also called 'retinol', is an essential nutrient. It is found in liver, eggs, dairy products, and most green leafy or orange fruit and vegetables. However, lack of vitamin A (vitamin A deficiency) is a common public health problem, especially in low-income countries. People with vitamin A deficiency may suffer from poor growth, an unhealthy immune system, night blindness and blindness. They are more likely to catch infectious diseases. Young children and pregnant women are most at risk.

In order to decide whether treatment with vitamin A supplements is needed or not, for individuals and communities, we need to know the existing levels of vitamin A deficiency. This requires accurate tests. Not recognising vitamin A deficiency when it is present may result in delayed or no vitamin A supplementation; vitamin A deficiency worsens, leading to scarring and vision problems. An incorrect diagnosis of vitamin A deficiency may mean that individuals are given vitamin A supplements when they are not needed, increasing the risk of vitamin A intake above recommended levels.

What tests measure vitamin A status?
The most accurate tests for vitamin A status (called the 'reference standards’) are liver biopsy and retinol isotope dilution. Liver biopsy involves removing a small sample of someone's liver and examining it under a microscope in a laboratory. Retinol isotope dilution involves giving a small dose of vitamin A and then examining a blood sample. These tests are invasive, costly, time-consuming, and technically demanding.

Other tests to measure a person’s vitamin A status are less invasive, less expensive, and quicker, but may not be so accurate. They are called 'index tests'. They look for signs of vitamin A ('biomarkers') in a blood sample. The most common tests are 'serum or plasma retinol' (SR) and 'serum or plasma retinol binding protein' (RBP). A positive test result indicates vitamin A deficiency, while a negative test result indicates the absence of vitamin A deficiency.

What did we want to find out?
We wanted to determine the accuracy of index tests compared with the reference standards for detecting vitamin A deficiency in people at risk of vitamin A deficiency.

What did we do?
We searched for studies that investigated the accuracy of the index tests compared to a reference standard and combined the results of the studies.

What did we find?
We included 40 studies that compared at least one index test and one reference test. Studies took place in North, Central and South America; Europe; South and Southeast Asia; and Africa. Participants were aged from 1 month to over 80 years. The percentage of people with vitamin A deficiency averaged between 4% and 60%. The results below are based on a hypothetical group of 1000 people.

SR versus retinol isotope dilution (23 studies)
In 1000 people where 100 (10%) have vitamin A deficiency measured with retinol isotope dilution, 82 people would have a SR result indicating vitamin A deficiency is present. Of these, 72 would be incorrectly classified as having vitamin A deficiency. Of the 918 people with a result indicating that vitamin A deficiency is not present, 90 would be incorrectly classified as not having vitamin A deficiency.

SR versus liver vitamin A (16 studies)
In 1000 people where 100 (10%) have vitamin A deficiency measured with liver vitamin A, 206 people would have a SR result indicating vitamin A deficiency is present. Of these, 153 would be incorrectly classified as having vitamin A deficiency. Of the 794 people with a result indicating that vitamin A deficiency is not present, 47 would be incorrectly classified as not having vitamin A deficiency.

RBP versus retinol isotope dilution (8 studies)
In 1000 people where 100 (10%) have vitamin A deficiency measured with retinol isotope dilution, 266 people would have a RBP result indicating vitamin A deficiency is present. Of these, 216 would be incorrectly classified as having vitamin A deficiency. Of the 734 people with a result indicating that vitamin A deficiency is not present, 50 would be incorrectly classified as not having vitamin A deficiency.

What are the limitations of the evidence?
Our confidence in the evidence is limited for several reasons. Most studies were small with little information about how they were done, so we couldn't judge how robust their methods were. Studies were not designed to determine the accuracy of index tests, so we need to be careful about interpreting their results. Finally, we didn't find information on all the tests.

How up to date is this review?
The evidence is up-to-date to August 2022.