Children’s risk of celiac disease continues five years after screening

February 9, 2022

Follow-up of Swedish school-age children with potential celiac disease finds 30 percent developed the condition

By Amy Ratner, director of scientific affairs

Children screened for celiac disease who have a positive blood test but then a negative biopsy continue to have a high risk of developing celiac disease and should be followed for five years, a recent Swedish study found.

About one third of children who participated in large-scale screenings for celiac disease and had positive blood tests but negative biopsies developed celiac disease within five years, according to the study by researchers from Umea University, Umea, Sweden.

Meanwhile, children who originally had a negative celiac disease blood test as part of the screenings had a very low risk of being diagnosed in the five-year follow up period.

Potential celiac disease

The children in the screenings who had positive anti-tissue transglutaminase (TTG) and endomysial antibody (EMA) tests and negative biopsies were classified as having potential celiac disease. Eleven of 35 children with potential celiac disease who returned for follow-up five years later were diagnosed with celiac disease.

The two original, school-based screenings of 12-year-olds in the general population included about 13,000 children. While 100 children had already been diagnosed with celiac disease, about 240 new cases were found, putting the number of undiagnosed children at more than  two thirds. The screenings were done in 2005-2006 and 2009-2010.

Researchers were interested in what happened to the children over time and invited them back for additional testing.

Some of the children with potential celiac disease had been diagnosed with celiac disease before the follow-up study, often because they developed symptoms. Others with potential celiac disease were not diagnosed until they received repeat TTG blood tests and biopsies as part of the follow-up. These children had symptoms that were so mild they did not lead to celiac disease testing prior to the follow up study.

“It is good for parents to know that there is a significant risk that their child will develop celiac disease in the years [following positive blood tests] and to see that follow-up [testing} is performed,” said Olof Sandström, MD, lead study author. “Of course we would like to know what could be done to prevent development from potential celiac disease to celiac disease, but we don’t have that knowledge yet.”

Negative blood test results

Only one child of the more than 12,000 originally found to have negative bloods tests through screening was later diagnosed with celiac disease.

The children who had negative blood tests were followed up through records in the National Swedish Childhood Celiac Disease Register to determine the risk for a clinical diagnosis. The nationwide register includes reports of new cases of celiac disease from all pediatric clinics that perform biopsies. Researchers identified one child from the first screening who had negative TTG but was later diagnosed with celiac disease. The child had type 1 diabetes, a risk factor for celiac disease, and had been tested annually as a result.

Repeat screening of children in this group could wait longer than five years, the study says. The authors note there are some limitations to that conclusion, including the possibility that while most cases of celiac disease are reported to the register, some may not be. Additionally, children in this group who were not tested again, particularly if they did not develop symptoms, might still have undetected celiac disease. Definitive information about these children would require a second screening, the authors wrote.


While it has been shown clinically that children who have positive celiac disease blood tests are at greater risk of eventually developing celiac disease, this study indicates the same is true within five years for children when they are identified as having potential celiac disease through general population screening, the authors note.

“In this study, we had the possibility to follow 39 cases of potential celiac disease for five years and found that about one-third developed celiac disease within this period,” the study says.

But the authors point out that there is a considerable difference when the first and second screening results are compared. In the first, the 12-year-olds were born in 1993, a period that has been identified as a celiac disease epidemic, and they had significantly higher prevalence at the follow up than among the second group of children, who were born in 1997. The first screening of about 7,600 children found 153 children with celiac disease and 29 with potential celiac disease, compared to the second screening of about 5,800 children which found 89 children with celiac disease and 10 with potential celiac disease.

“We cannot exclude that environmental factors increasing the risk for celiac disease also affected risk for potential celiac disease and conversion [from potential celiac disease] to celiac disease,” the study says.

The Swedish celiac disease epidemic was partly explained by changes in infant feeding, according to a 2009 study by a group of Swedish hospitals and universities. In Sweden, parents of almost all infants attend well-baby clinics for which they have a high level of confidence, and changes in dietary recommendations are thereby effectively implemented,” the study says. “Before the epidemic, a national recommendation was made to postpone introduction of gluten from four to six months of age, an interval during which breast-feeding was often discontinued.”

Coincidentally, at the same time the gluten content of commercially available milk cereal drinks and porridges was increased, the study says. When the epidemic ended it was preceded by a recommendation to introduce gluten gradually, preferably while still breast-feeding, as well as a reduction in the gluten content in commercially available infant foods.

Limitations of the recent follow-up study include the relatively small number of potential celiac disease cases and lack of total participation in the follow-up, which the authors wrote could have resulted in underestimation of prevalence.

Study authors also point out that the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) allows for a celiac disease diagnosis in children without a biopsy if their TTG level is ten times the upper limit of normal.

Applying these guidelines to the follow-up, one child could have been diagnosed without the biopsy, the study says.

In the United States, the North American Society for Pediatric Gastroenterology guidelines recommend a biopsy for confirmation of a diagnosis of celiac disease.

Authors of the study have previously investigated screening of children in the general population, including studies regarding the use of high levels of TTG antibodies in children to diagnose celiac disease without a biopsy and the cost effectiveness of screening Swedish 12-year-olds.

They have concluded that a population-based screening is the only way to find most coeliac disease cases, in part because symptoms can be vague and challenging to identify in clinical practice.

Screening in the United States

Screening is the process of testing for a disease in those who do not have symptoms that would indicate they have the condition. Screening tests can be done individually when someone visits their doctor or in a large group, as was done through the schools in the Swedish screening study. Large scale screening is often done in the general population.

In 2017, the U. S. Preventative Services Task Force concluded there is insufficient evidence to assess the balance of benefits and harms of screening for celiac disease in those who do not have symptoms. The task force is a panel of experts in disease prevention that works to improve the health of Americans by making evidence-based recommendations about clinical preventive services.

A subsequent study of nearly 10,000 children in Colorado concluded that universal screening may be the only way to identify all the children in the United States who have celiac disease.

The study by researchers at University of Colorado also found that symptoms were not reliable predictors of which children would have celiac disease. And most children who had positive antibody screening did not have a family history of celiac disease.

You can read more about the recent Swedish study here and the US screening study here.

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