Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State

Abstract

Background: High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia.Material and methods: In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia.Results: Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (≥4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8).Conclusion: This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.

Figure 1.

Illustration of restricted cubic spline models for the association of age at diagnosis, birthweight, size for gestational age, and Ponderal index with five-year all-cause mortality risk in 7148 children and adolescents with leukemia from Denmark, Norway, Sweden, and Washington State, 1967–2015.