Birth characteristics and childhood leukemia in Switzerland: a register-based case\u2013control study

Judith E Lupatsch,Christian Kreis,Ben D Spycher,Marc Ansari,Claudia E Kuehni,Garyfallos Konstantinoudis

doi:10.1007/s10552-021-01423-3

Abstract

PurposeInitial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth.MethodsWe identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0–15 and 0–4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).ResultsThe study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12–1.69) and multiple birth (1.89, 1.24–2.86). These associations were similar for ALL and stronger for leukemia at ages 0–4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43–22.03 for fourth or later born children). We found no associations with other perinatal characteristics.ConclusionThis register-based case–control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.

Highlights

Both genetic and environmental factors are suspected to play a role in the etiology of childhood leukemia [1, 2]
The prevalence of high birth weight (≥ 4000 g, 10.5% vs. 8.2%) and multiple birth (3.5% vs. 2.2%) was higher than among controls; 49 cases were born as part of a twin pair (Table S1)
We found strong positive correlations between birth order and interval to older sibling and between maternal and paternal age, and a negative correlation between multiple birth and birth weight (Fig. S1)

Summary

Introduction

Both genetic and environmental factors are suspected to play a role in the etiology of childhood leukemia [1, 2]. High birth weight is an established risk factor for childhood leukemia and ALL [29,30,31,32]. Recent studies have consistently shown positive associations between high birth weight relative to gestational age [33]. Some early studies suggested that multiple birth may protect against later development of childhood leukemia [34, 35]. These findings could not be reproduced in recent studies that consistently adjusted for birth weight [20, 36]

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