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In health-related fields, a reference range (or reference values or interval) is a set of values of some measurement that a physician or other health professional can use to interpret a set of results for a particular patient. It is determined by collecting data from vast numbers of laboratory tests.

Contents

Standard definition

A reference range for a particular test or measurement, is usually defined as the prediction interval of values that 95% (or 2 standard deviations) of the population fall into. It relies on the fact that for many biological phenomena, there is a normal distribution of values.

It is commonly referred to as the normal range or normal values (and sometimes "usual" range/values). However, this term should be discouraged as not everyone outside the range is abnormal, and people who have a particular condition may still fall within this range.

In some cases, reference ranges are better based on concentrations or levels that are associated with optimal health or minimal risk of related complications and diseases, rather than the standard reference described above (See Optimal health range section below).

Regarding population, if not otherwise specified, it generally denotes the reference range in healthy individuals, or without any known condition that directly affects the ranges being established. However, reference ranges may also be established by taking samples from the whole population, with or without diseases and conditions. In some cases, diseased individuals are taken as the population, establishing reference ranges among those having a disease or condition.

Reference ranges may also be specified to subgroups of a healthy population to compensate for individual differences in age, sex, race etc, where there otherwise could be a bimodal distribution. Common distinctions are differences between males and females and age (such as prostate specific antigen).

Some reference ranges have further mathematical functions applied to the original values, e.g. where there is log-normal distribution rather than usual normal distribution.

A graphical illustration

Normaldist95.png

In an ideal situation, where the distribution is normal, the reference range can be obtained by simply measuring a population and taking two standard deviations either side of the mean.

Bimodal.png

If a normal population shows a bimodal distribution, it is useful to find out why this is the case. Two reference ranges can be established for the two different groups of people. (This pattern is commonly seen in tests that differ between men and women, but could conceivably be seen in a bicultural society and other situations.)

Inaccuracy

  • The reference range will vary, depending on the age, sex and race of a population, and even the instruments the laboratory uses to perform the tests. To compensate, individual laboratories have their own lab ranges to account for the instruments used in the laboratory and local differences in the population.
  • The whole concept of reference ranges assumes a normal distribution of samples, and gets inaccurate when samples actually deviate from normal distribution, e.g. having bimodal distribution. Still, in the case of differences between females and males, they may be split into separate groups, each one showing higher degree of normal distribution.
  • Reference ranges only denote what are usual values in the population, and do not directly correlate with the ranges for optimal health (see Optimal health range section below).
  • Reference ranges are also affected by diet, use of drugs (prescribed, over-the-counter and herbal remedies), and stress, as well as other more exotic factors like altitude.
  • The test procedure itself may be erroneous or inaccurate. Therefore, every test outside the reference range should be repeated if possible.

Optimal health range

Optimal (health) range or therapeutic target (not to be confused with biological target) is a reference range or limit that is based on concentrations or levels that are associated with optimal health or minimal risk of related complications and diseases, rather than the standard range based on normal distribution in the population.

It may be more appropriate to use for e.g. folate, since approximately 90 percent of North Americans may actually suffer more or less from folate deficiency, [1] but only the 2.5 percent that have the lowest levels will fall below the standard reference range. In this case, the actual folate ranges for optimal health are substantially higher than the standard reference ranges. Vitamin D has a similar tendency. In contrast, for e.g. uric acid, having a level not exceeding the standard reference range still does not exclude the risk of getting gout or kidney stones.

Examples

Reference ranges for blood tests, sorted by mass and molar concentration.

See also

References

  1. ^ Folic Acid: Don't Be Without It! by Hans R. Larsen, MSc ChE, retrieved on July 7, 2009. In turn citing:
    • Boushey, Carol J., et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Journal of the American Medical Association, Vol. 274, October 4, 1995, pp. 1049- 57
    • Morrison, Howard I., et al. Serum folate and risk of fatal coronary heart disease. Journal of the American Medical Association, Vol. 275, June 26, 1996, pp. 1893-96
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