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

Abstract 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.

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Neuropsychological late effects of treatment for acute leukemia in children with Down syndrome

Pediatric Blood & Cancer ◽

10.1002/pbc.25362 ◽

2014 ◽

Vol 62 (5) ◽

pp. 854-858 ◽

Cited By ~ 4

Author(s):

Caroline Roncadin ◽

Johann Hitzler ◽

Andrea Downie ◽

Isabelle Montour-Proulx ◽

Cheryl Alyman ◽

...

Keyword(s):

Down Syndrome ◽

Acute Leukemia ◽

Late Effects ◽

Children With Down Syndrome ◽

Leukemia In Children

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Very High Birth Weight of Offspring Is Associated with an Increased Risk of Leukemia in Their Mothers; Results of a Population-Based Cohort Study.

Blood ◽

10.1182/blood.v110.11.4677.4677 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4677-4677

Author(s):

Ora Paltiel ◽

Rebecca Yanetz ◽

Ronit Calderon ◽

Orly Manor ◽

Susan Harlap ◽

...

Keyword(s):

Birth Weight ◽

Maternal Age ◽

Childhood Leukemia ◽

Demographic Data ◽

Population Based ◽

Continuous Variable ◽

High Birth Weight ◽

Average Birth Weight ◽

Multivariate Adjustment ◽

Increased Risk

Abstract High birth weight (HBW) is related to maternal diabetes, height, BMI and weight gain during pregnancy. Many previous studies have shown an association between HBW and childhood leukemia. Postulated mechanisms have included exposure to growth factors involved in somatic growth and leukemogenesis (e.g. IGF-1), common genetic mechanisms or higher cell number in larger individuals providing increased opportunity for genetic errors. It is not known to what extent the association is due to heritable factors, intra-uterine factors or both. To our knowledge, the association between offspring’s birth weight and leukemia risk in the parents has not been addressed. Methods: We utilized data from the Jerusalem Perinatal Study, a population-based research cohort including all births in West Jerusalem between 1964 and 1976. The database contains information on birth characteristics of the newborns, obstetric complications and birth outcomes as well as demographic data on the parents. After excluding the parents of twins and offspring with congenital malformations, we linked 39,336 mothers and 38,031 fathers of live-born infants through their unique identification numbers to the Israel Cancer Registry. We examined the association between leukemia and the average birth weight of all offspring of the same mother or father, as a categorical and continuous variable, as well as the effect of having at least one offspring weighing ≥4500 gm. Fewer than 2% of parents had offspring weighing 4500 gm or more. Results: Leukemias developed in 57 mothers and 132 fathers. Controlling for maternal age, having at least 1 child weighing ≥4500 gm at birth was associated with a 3-fold increase in the risk of leukemia (hazard ratio -HR 3.4, 95% confidence interval (CI) 1.06–10.91, p=0.04), compared to having no children at the extremes of birth weight. This result was unchanged after multivariate adjustment. Furthermore having an average birth weight among all offspring of ≥4500 gm increased the risk of leukemia in mothers more than 8 fold (HR 8.3, 95% CI: 2.5–27.7, p=0.0006), after controlling for maternal age and diabetes, compared to an average birth weight of 2500–3999 gm. This result was strengthened after further multivariate adjustment for family size and socioeconomic status (HR 8.99, 95%CI: 2.8–29.27, p=0.001). In a subgroup for which these data were available (∼13,000 mothers), results were unchanged after adjusting for maternal height. Birth weight assessed as a continuous variable was not related to mother’s leukemia. Specific subgroups of leukemia in the mother which were associated with HBW were CLL (HR 11.04, p=0.002) and CML (7.84, p=0.05) but these analyses were severely limited by small numbers. There was no association between HBW and father’s risk of leukemia. Conclusions: HBW is associated with leukemia not only in infants and children, but appears to confer an increased risk among their mothers. Whether this is due to a common exposure (eg pelvic irradiation), shared genes, or epigenetic phenomena bears exploring, after confirmation of these results in other cohorts.

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Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome

Cancer ◽

10.1002/cncr.23025 ◽

2007 ◽

Vol 110 (9) ◽

pp. 2067-2074 ◽

Cited By ~ 18

Author(s):

Susan E. Puumala ◽

Julie A. Ross ◽

Andrew F. Olshan ◽

Leslie L. Robison ◽

Franklin O. Smith ◽

...

Keyword(s):

Down Syndrome ◽

Acute Leukemia ◽

Infertility Treatment ◽

Reproductive History ◽

Children With Down Syndrome ◽

Leukemia In Children

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Infections and Acute Leukemia in Children with Down Syndrome

Prenatal Diagnosis and Screening for Down Syndrome ◽

10.5772/18533 ◽

2011 ◽

Cited By ~ 1

Author(s):

Juan Manuel ◽

Maria Luisa ◽

Janet Flores-Lujano ◽

Carolina Bekker ◽

Sandra Pinto-Cardoso ◽

...

Keyword(s):

Down Syndrome ◽

Acute Leukemia ◽

Children With Down Syndrome ◽

Leukemia In Children

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Maternal health conditions during pregnancy and acute leukemia in children with Down syndrome: A Children's Oncology Group study

Pediatric Blood & Cancer ◽

10.1002/pbc.21914 ◽

2009 ◽

Vol 52 (5) ◽

pp. 602-608 ◽

Cited By ~ 9

Author(s):

Simona Ognjanovic ◽

Susan Puumala ◽

Logan G. Spector ◽

Franklin O. Smith ◽

Leslie L. Robison ◽

...

Keyword(s):

Down Syndrome ◽

Maternal Health ◽

Acute Leukemia ◽

Health Conditions ◽

Oncology Group ◽

Oncology Group Study ◽

Children With Down Syndrome ◽

Leukemia In Children

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GATA1 mutations in acute leukemia in children with Down syndrome

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2005.10.008 ◽

2006 ◽

Vol 166 (2) ◽

pp. 112-116 ◽

Cited By ~ 16

Author(s):

Isis Quezado Magalhães ◽

Alessandra Splendore ◽

Mariana Emerenciano ◽

Alexandre Figueiredo ◽

Íris Ferrari ◽

...

Keyword(s):

Down Syndrome ◽

Acute Leukemia ◽

Children With Down Syndrome ◽

Leukemia In Children

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Magnetic Fields and Acute Leukemia in Children With Down Syndrome

Epidemiology ◽

10.1097/01.ede.0000248186.31452.be ◽

2007 ◽

Vol 18 (1) ◽

pp. 158-161 ◽

Cited By ~ 25

Author(s):

Juan Manuel Mejia-Arangure ◽

Arturo Fajardo-Gutierrez ◽

Maria Luisa Perez-Saldivar ◽

Clara Gorodezky ◽

Armando Martinez-Avalos ◽

...

Keyword(s):

Down Syndrome ◽

Magnetic Fields ◽

Acute Leukemia ◽

Children With Down Syndrome ◽

Leukemia In Children

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Immune-Related Conditions and Acute Leukemia in Children with Down Syndrome: A Children's Oncology Group Report

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-14-1181 ◽

2014 ◽

Vol 24 (2) ◽

pp. 454-458 ◽

Cited By ~ 3

Author(s):

Amy M. Linabery ◽

Wenchao Li ◽

Michelle A. Roesler ◽

Logan G. Spector ◽

Alan S. Gamis ◽

...

Keyword(s):

Down Syndrome ◽

Acute Leukemia ◽

Oncology Group ◽

Children With Down Syndrome ◽

Group Report ◽

Leukemia In Children

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In Utero Diagnoses of Strikingly Similar Presentations of Complete Atrioventricular Septal Defects in a Pair of Dizygotic Twins Concordant for Trisomy 21

Case Reports in Pediatrics ◽

10.1155/2018/6215675 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Diamond Ling ◽

Jonathan G Dayan

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Heart Disease ◽

Trisomy 21 ◽

Maternal Age ◽

Congenital Heart ◽

Genetic Disorder ◽

Advanced Maternal Age ◽

Dizygotic Twins ◽

Increased Risk

Trisomy 21, or Down syndrome (DS), is a genetic disorder affecting approximately 1 in 500–750 live births. The prevalence of DS has increased over the past two decades, correlating with a rise in the proportion of pregnancies complicated by advanced maternal age. There is also a correlation between advanced maternal age and dizygotic twinning rates. There is an increased risk of at least one twin being affected in dizygotic pregnancies compared to singletons. However, despite this greater relative risk, reports of concordance of DS in both dizygotic twins are very rare. Congenital heart disease (CHD) occurs in roughly 40% of individuals with DS, but there can be considerable phenotypic variation. The most common, atrioventricular septal defect accounts for only 40% of CHD seen in DS. There is also a higher incidence of CHD in twins, but also with a low incidence of concordance. There have been only five reported cases of concordant DS in dizygotic twins with confirmed chromosomal analyses; none of which describe concordant congenital heart disease. Here, we describe an unusual case of dizygotic twins of differing genders concordant for both Down syndrome and congenital heart disease of a strikingly similar presentation.

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