Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome: a report from the Children's Oncology Group.
BACKGROUND
Children with Down syndrome (DS) have from 10 to 20 times the risk of developing acute leukemia than the general pediatric population. There is mixed evidence for associations between reproductive history or infertility and acute leukemia among children without DS.


METHODS
The authors conducted a case-control study of acute leukemia among children with DS to investigate possible risk factors in this population. From 1997 to 2002, 158 children aged <20 years with DS who had a diagnosis of acute leukemia (97 children with acute lymphoblastic leukemia [ALL] and 61 children with acute myeloid leukemia [AML]) were enrolled at Children's Oncology Group (COG) institutions. Controls with DS (n = 173) were selected from the cases' primary care clinic and frequency matched to cases on age. Telephone interviews were conducted with mothers of cases and controls assessing reproductive history, infertility, and infertility treatment.


RESULTS
Null results were observed overall and by subtype for reproductive factors, including previous pregnancy outcomes and contraceptive use, and for most infertility outcomes. There was an increased risk of AML among children with DS whose parents had ever tried for >/=1 year to become pregnant (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.14-4.33). A 1-year increase in maternal age also was associated with AML (OR, 1.06; 95% CI, 1.01-1.12).


CONCLUSIONS
Although the questionnaire was limited in this area, the results suggested that the risk for AML may be raised in children with DS because of infertility. In that the risk of infertility, along with having a child with DS, increase with age, these results warrant more research.
Puumala
Susan E
SE
Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Ross
Julie A
JA
Olshan
Andrew F
AF
Robison
Leslie L
LL
Smith
Franklin O
FO
Spector
Logan G
LG
D000208:Acute Disease; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications*; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects; D005307:Fertilization in Vitro / Q000009:adverse effects; D006801:Humans; D007246:Infertility / Q000628:therapy*; D007938:Leukemia / Q000150:complications*; D008297:Male; D008423:Maternal Age; D009035:Mothers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017584:Reproductive History; D012307:Risk Factors; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects
D005300:Fertility Agents, Female