Maternal and Birth Characteristics and Risk of Leukemia in Children with Down Syndrome.

High birth weight (> 4000 g) is a risk factor for childhood leukemia, especially for younger children. Advanced maternal age has also been associated with an increased risk, though less consistently than birth weight. Because children with Down syndrome (DS) are at a 20-fold increased risk of developing acute leukemia than the general population, we evaluated maternal and child birth characteristics that may be associated with leukemia in children with DS. A case-control study of DS and acute leukemia was conducted through the Children’s Oncology Group in North America. From 1997 to 2002, 158 children ages birth-18 years with DS and acute leukemia (including 61 acute myeloid leukemia (AML) and 97 acute lymphoblastic leukemia (ALL)) were enrolled. Children with DS alone (n= 173) were identified through the cases’ pediatric clinics and frequency matched to cases on age. Mothers of cases and controls completed a telephone interview that included questions regarding maternal and birth characteristics. Here, we present data related to singleton pregnancies (165 controls and 151 cases (96 ALL/55AML)). Advanced maternal age (≥ 35 vs. <35) was associated with an elevated risk of leukemia (Odds Ratio (OR)=1.79, 95% Confidence Interval (CI))=1.09–2.94), which was apparent for both ALL and AML. There was also a suggestion of an increased risk for children in the highest tertile (>3260 g) of birth weight (OR=1.56, 95% CI=0.87–2.78) compared to children in the reference group (2850–3260 g). Birth length ≥ 21 inches showed an increased risk for AML cases only (OR=3.06; CI=1.25–7.50). In contrast, increasing birth order was associated with a decreased risk, particularly for AML (OR=0.36; 95% CI 0.14–0.97). This is the first study to evaluate maternal and child birth characteristics in relation to leukemia risk in children with DS. Our results add to the growiA. ng body of evidence that suggests that newborn body size may be related to the underlying etiology of childhood leukemia.