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Maternal infection may increase childhood leukaemia risk: Study

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Children whose mother had an infection during pregnancy may have a 35% increased risk of leukaemia, newly published Australian and international research has found.
 
The Danish cohort study involved 2.2 million children, and assessed the link between infection during pregnancy and childhood cancer, finding that the leukaemia risk was especially high for those whose mothers had a genital tract infection or UTI.
 
No link was found for respiratory tract, digestive, or other infections, and there was no link between maternal infection and brain tumours, lymphoma, or other childhood cancers.
 
However, relative leukaemia risk increased by 142% following maternal genital tract infections, and 65% after a UTI.
 
While the absolute risk of developing leukaemia among this cohort remains small and further studies are needed to confirm these links, the authors say the findings have implications for ‘understanding of the causes of childhood leukaemia and potential preventive measures’.
 
Dr Wendy Burton, Chair of RACGP Specific Interests Antenatal and Postnatal Care, told newsGP the study sheds some light on care during pregnancy and preventing risk.
 
‘It’s too soon to know for sure, but research like this is interesting, and it reminds us of the importance of considering what is this condition – in this case an infection – doing to the pregnant person and what is it doing to the unborn child?’ she said.
 
‘For GPs, there is ongoing importance of considering the whole person and their future. Identifying and treating conditions as they arise is important, whether it is an infection, or asthma or a mood disorder.’
 
Using data from seven Danish national birth, patient and cancer registries from 1978–2015, the researchers analysed results from a four-year follow-up period of December 2019 to December 2021, including that of siblings who showed ‘comparable estimates’ to the whole-cohort analysis.
 
From the 2.2 million participants – comprised of an almost even gender balance (51.3% boys and 48.7% girls) – a total of 4362 children were diagnosed with cancer before age 15 years.
 
This included 1307 leukaemia diagnoses, comprising 1050 acute lymphoid leukemia cases, 165 acute myeloid leukemia cases, and 92 other types.
 
Around 81,717 pregnant people had at least one type of infection during pregnancy, including:

• 37,522 UTIs
• 14,382 genital tract infections
• 10,097 digestive system infections
• 7318 respiratory tract infections.

Compared to those with no infections, those with any infection during pregnancy were more likely to:
 

• be pregnant for the first time
• be slightly younger
• have a higher pre-pregnancy BMI
• have diabetes
• smoke during early pregnancy
• deliver preterm and low birth weight infants.

Previous research suggests that childhood leukaemia may originate in utero, and the Danish study findings support that immune-related factors during pregnancy may be involved in the development of childhood leukaemia.
 
‘If confirmed in future studies, our findings may have implications for understanding the aetiology and developing preventive measures for childhood leukemia,’ the authors wrote.
 
Experts evaluating the study note that while the results present significant implications for understanding risks and causes of leukaemia, there are some limitations to consider.
 
‘The study relied on registry data, which may not have captured all relevant information, such as specific types of infections or the severity of the infections,’ Associate Professor Alex Polyakov, a consultant obstetrician, gynaecologist and fertility specialist at Melbourne’s Royal Women’s Hospital said.
 
‘Secondly, the study did not differentiate between bacterial and viral infections, which may have different effects on fetal development. Thirdly, the study did not investigate potential mechanisms underlying the association between maternal infection and childhood leukaemia.
 
‘It must also be pointed out that childhood leukaemia, the most common childhood cancer, is a rare condition. The increase in risk, while statistically significant, translates into only a very small increase in the number of children who may develop the disease.’
 
Dr Helen Bailey from Curtin University Medical School agrees that the findings of the study add to what is known about the origins of leukaemia, but more research is needed.
 
‘[The study backs evidence that leukaemia] may be triggered by events before birth or in early life,’ she said.
 
‘While exciting, the findings of this study need to be verified by research in other populations and about possible mechanisms.’
 
Dr Burton also hopes to see more findings in this area.
 
‘I will be interested in the follow-up research,’ she said.
 
‘The absolute numbers will of course be small, but the relative increase in risk is significant.’
 
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childhood cancer genital tract infection leukaemia maternity care UTI

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