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Leukaemia and Down's Syndrome Linked in Infants Whose Mothers Underwent Fertility Treatments: Presented at AACR

By Cameron Johnston

LOS ANGELES, CA -- April 16, 2007 -- It is well known that a woman's age increases her risk of her having a child with Down's syndrome. Now, a study presented here at the American Association for Cancer Research (AACR) annual meeting suggests that children with Down's syndrome have a greater risk of developing leukaemia if their mother underwent any kind of fertility treatment.

In this study, the risk of leukaemia, specifically acute myeloid leukaemia (AML), was 2.5 times greater (odd ratio = 2.47, 95% CI, 1.02 - 5.97) among children with Down's syndrome whose mothers had tried to conceive for more than a year, according to Susan Puumala, PhD candidate in childhood cancers, University of Minnesota, Minneapolis, Minnesota, United States.

Among mothers who had undergone surgical fertility treatments (including in vitro fertilisation) the odds ratio increased to 2.78, the researcher said in an interview.

Leukaemia occurs in approximately one in 150 children with Down's syndrome and has a severe impact on the children's already fragile health profile, Puumala said. Prior studies have already indicated a moderately elevated risk of developing AML in infants of mothers with prior foetal loss, longer intervals between births and older age, she added.

The link between risk of leukaemia and fertility treatments has not previously been studied in any major way.

Between 1997 and 2002, Puumala and colleagues enrolled 158 children with Down's syndrome who were younger than 20 years and were living in Canada or the U.S. at enrolment and were registered with the Children's Oncology Group, a worldwide organization aimed at studying childhood cancers. Control subjects who did not have leukaemia were selected from the cases' primary care clinic and were frequency matched to cases based on age (n = 173).

The researchers conducted telephone interviews with the mothers of leukaemia/Down's children and with parents of control subjects. The analysis specifically looked at reproductive history, infertility treatments and the risk of any form of leukaemia.

There was little evidence of any kind of association for most of the variables studied. However, risk of the child having leukaemia increased according to the length of time it took the mother to become pregnant, and increased even more when the mother underwent any form of fertility treatment.

Women who used fertility treatments other than medical or surgical approaches had the highest risk of all (OR = 3.31, 95% CI = 0.81-13.57). The specific forms of assisted reproduction were not itemised in the questionnaire. Mothers were only asked whether they used medical fertility treatments, surgical treatments, or other treatments.

There was no increased risk if the mother was under the age of 30 years, but risk increased to 1.23 (odds ratio) if she was between the ages of 30 and 34 and it increased to 2.63 if she was over 35 years of age.

The data was adjusted for maternal age, race of the mother and education. The analysis was conducted for all forms of leukaemia and stratified for acute lymphoblastic leukaemia (n = 97) and AML (n = 61).

"Although our questionnaire was limited in this area of the enquiry, these results suggest that the risk of AML may be increased in children with Down's syndrome whose mothers used infertility treatments," she said.

Given that mothers who are 35 years of age or older are probably going to receive some form of counselling about the risk of Down's syndrome when they are planning to have a baby, this finding suggests that they should also be advised of the potential risk of leukaemia in the child if they undergo fertility treatment.

This could suggest that more children "who are conceived as a result of assisted reproduction nay be at greater risk for chromosomal and epigenetic defects" that are caused in some way by fertility treatments, but this hypothesis requires much more research, she added.

The study was funded by the National Institutes of Health and the Children's Cancer Research Fund.


[Presentation title: Reproductive History, Infertility Treatment, and the Risk of Acute Leukaemia in Children With Down Syndrome: A Report From the Children's Oncology Group (COG). Abstract 96]

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