Infection during pregnancy associated with increased incidence of leukaemia among children

Breaking new ground 30. mar 2023 2 min DPhil Jian-Rong He Written by Kristian Sjøgren

Women who have a genital or urinary tract infection during pregnancy have an increased risk of their child developing leukaemia later in life. However, a researcher says that the absolute risk is still so low that the study does not warrant a change in clinical practice.

Leukaemia is the most common type of cancer among children, and now a new study shows that this leukaemia may be associated with an infection experienced by the mother during pregnancy.

The registry study of more than 2.2 million children born in Denmark shows that children born to mothers with infection in pregnancy had an increased risk of leukaemia.

Genital and urinary infections appear to be especially associated with a strongly increased risk of the child developing leukaemia.

However, a researcher behind the study says that the absolute risk of the child developing leukaemia remains very low – even if the mother has an infection during pregnancy.

“Our results do not warrant an immediate change in clinical practice, since the risk of children developing leukaemia is still very low and the findings need confirmation in future studies. But our study may contribute to understanding the aetiology of leukaemia among children,” explains Jian-Rong He, a researcher from Guangzhou Women and Children’s Medical Center, China and Department of Women’s and Reproductive Health, University of Oxford, United Kingdom.

The research has been published in JAMA Network Open.

Data on 2.2 million children

The researchers examined databases in Denmark and identified 2,222,797 children born from 1978 to 2015.

Denmark’s registry data are among the most complete in the world and therefore ideal for studying links between diseases.

The researchers identified which mothers had been diagnosed with an infection during pregnancy, including urinary tract infection, genital infection, respiratory infection, digestive system infection or other infection.

The researchers followed the children for an average of 12 years and identified 1307 diagnoses of leukaemia.

3.7% of the mothers had had an infection during pregnancy: urinary tract, 1.7%; genital , 0.7%; digestive system, 0.5%; and respiratory, 0.3%.

The mothers diagnosed with an infection tended to be younger and had fewer years of education, higher prepregnancy body mass index, a higher prevalence of diabetes and a higher prevalence of smoking in early pregnancy. They also more often gave birth preterm and gave birth to children with low birth weight.

The researchers compared the risk of developing leukaemia among the children of mothers with versus without an infection during pregnancy.

Infections associated with increased risk of leukaemia

The children of mothers with an infection during pregnancy had a 35% increased risk of developing leukaemia.

In particular, genital infections among mothers were associated with a 142% increased risk of leukaemia among children and urinary tract infections with a 65% increased risk.

The researchers found no association between infections in the respiratory tract or the digestive system or other infections and the child’s risk of developing leukaemia.

The researchers found that a genital or urinary tract infection was associated with acute lymphoid leukaemia and chronic myeloid leukaemia similar to the association with leukaemia.

The researchers confirmed their findings in a subgroup analysis by examining data on children born to the same mother: comparing the risk between siblings exposed to maternal infection and siblings without such exposure.

The researchers also confirmed their findings in registry data for all births in Sweden from 1988 to 2014.

“Researchers have for many years wondered whether infection during pregnancy could be associated with leukaemia among children. This has been investigated in several studies, but the results have been ambivalent. This study shows an association in a large data set,” says Jian-Rong He.

He elaborates that the researchers found no association between infections during pregnancy and other types of cancer among the children.

“This suggests that infection during pregnancy specifically only affects the risk of developing leukaemia among children,” adds Jian-Rong He.

Further studies required

Jian-Rong He says that the reasons for the association between infection during pregnancy and the child’s risk of developing leukaemia are still unclear.

One possibility is that localised inflammation may be an important potential cause of genetic and immune abnormalities in fetuses, and future studies may elucidate this.

“Future epidemiological studies in different regions and mechanistic research are needed to confirm our findings and investigate the underlying mechanisms behind the association. These studies can help us to understand the background for children developing leukaemia and perhaps also determine how to prevent this,” concludes Jian-Rong He.

Evaluation of maternal infection during pregnancy and childhood leukemia among offspring in Denmark” has been published in JAMA Network Open. In 2018, the Novo Nordisk Foundation awarded a grant to co-author Jiong Li for the project Prenatal Parental Diabetes and Long-term Health Outcomes in Offspring: a Multinational Register-based Study in Five Nordic Countries.

My research areas focus on maternal and child health epidemiology. I am involved in several large-scale cohort studies, such as the Born in Guangzhou...

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