New research that examined more than 300 million laboratory test values from nearly 2 million people shows that some test values from hospital laboratories can vary considerably during the year. The researchers say that doctors should consider seasonally adjusted reference intervals when assessing whether test results may indicate disease.
Seasonal variation in some of the test results produced by hospital laboratories is well documented.
One example is seasonality in vitamin D concentration, and other values also vary because people consume more fatty food and sugar in December or more fresh fruit and vegetables in the summer.
A new study based on data from more than 300 million measurements for nearly 2 million hospital patients in Denmark shows seasonality in many more laboratory values than just vitamin D. Of 1,545 unique laboratory test results, 110 showed significant seasonality.
The study may affect the reference values that doctors use to determine whether laboratory values are within the normal range or too high or too low and thus may indicate disease.
“Our research indicates that the reference intervals for these 110 laboratory values should take into account the seasonal variation, so that doctors can better interpret the laboratory results they receive. By using seasonally adjusted reference values, doctors can make more precise diagnoses and thus perhaps ultimately also reduce mortality,” explains a researcher behind the study, Søren Brunak, Research Director and Professor, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.
The research has been published in Patterns.
Data from nearly 2 million people
The researchers obtained data on everyone who had a laboratory test performed in connection with hospitalisation in the Capital Region of Denmark or Region Zealand over a period of 6 years.
The data were derived from 1,987,180 unique patients, resulting in 310,455,299 usable unique quantitative measurements, corresponding to 1,545 unique laboratory tests.
The researchers cleaned and prepared the data to analyse whether there was any seasonality.
Seasonality could potentially be related to seasons, to specific times, such as around Christmas or summer, or to other yearly trends, such as financial spending.
The researchers asked a computer to find patterns and did not start with any assumptions.
The researchers also examined differences in laboratory values between the sexes and across age groups.
“What is also interesting is that these data are at the population level: data from children and young and older adults. They are from all patients hospitalised or discharged from a hospital in the two health regions. Much of the work involved preparing and harmonising the data, since the hospitals do not necessarily use the same systems or codes for all the different tests,” says another researcher behind the study, Victorine Muse, PhD Fellow, Novo Nordisk Foundation Center for Protein Research.
Seasonality in 110 laboratory values
Many laboratory test results showed seasonal variation.
This applies to vitamin D and thyroid-stimulating hormone, which is not surprising, since these two values are well known to vary throughout the year.
The researchers also found seasonality in vitamin B12, the level of which is usually associated with meat intake since meat is the main dietary source. According to Søren Brunak and Victorine Muse, the seasonal variation can result from people eating less meat in the summer and more fruit and vegetables.
In addition, long-term blood glucose had seasonality, especially for middle-aged women, which may be related to menopause.
“We found 110 laboratory values that showed statistically significant seasonality. This means that the reference intervals for the normal values for these 110 values should not be fixed but instead follow the seasons and be slightly modified,” explains Søren Brunak.
Correcting for seasonality provides more accurate results
Søren Brunak explains that the laboratory results on Denmark’s health platform Sundhed.dk may be labelled black or red.
Black values are within the normal range, and red values are higher or lower.
According to Søren Brunak, Sundhed.dk could use seasonally adjusted and sex-corrected reference values rather than fixed values to provide more precise information for citizens and doctors.
“For example, when long-term blood glucose, a marker for diabetes, shows seasonality, values may be within the normal range at certain times of the year and outside the normal range at other times. This should be reflected in the reference values that both Sundhed.dk and general practitioners use,” says Søren Brunak.
He elaborates that doctors are already aware of when vitamin D concentrations are normally low or high, but this may be more difficult for other values.
In addition, doctors are not the only ones to look at the values in the laboratory test results.
“For doctors, this will improve their opportunities to diagnose more accurately and rapidly, and health data scientists, who do not necessarily always know what the values mean, will create better health models more easily when they include seasonally adjusted laboratory values in developing the models,” says Søren Brunak.
Seasonally corrected values may save lives
The researchers also showed that using seasonally adjusted reference values in diagnosis can have positive health effects.
In one analysis, the researchers investigated whether using seasonally adjusted instead of fixed reference values would affect diagnosis and mortality. The diagnoses and survival correlate better using the seasonally adjusted reference values and the sex-corrected reference values. The reference values should not be changed for the values that do not change much over the year.
“The values are directly correlated with the health of men and women and should be considered in diagnosis and treatment. For example, we found that cardiac troponin, which is used to diagnose blood clotting in the heart, shows seasonal variation and gender variation. Independently of our study, researchers and doctors are currently investigating in clinical trials whether new reference values should be created based on both sex differences and seasonality,” concludes Victorine Muse.