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.

Ethical approval

The study was approved by the Data Protection Agency in Denmark (Record no. 1-16-02-484-14); the Regional Committee for Medical and Health Research Ethics of South East Norway (Record no. 2016/607); the Regional Ethics Committee, Stockholm, Sweden (Record no. 2012/298-31/1); and the Institutional Review Board of Washington State (Record no. D-082312-H13.03) and the Fred Hutchinson Cancer Research Center (#479) in the USA.

Danish law does not require an ethical approval or an informed consent from patients for studies based on routinely collected registry data.

The study was performed in accordance with the Declaration of Helsinki. The study did not involve any patients since this was a purely registry-based study.

Author contributions

A.G.O., A.E., and H.T.S. conceived the study idea and designed the study. Authors of the respective countries acquired the country-specific data. L.B.C. carried out the analyses. A.G.O. organized the writing and wrote the initial draft. All authors participated in the discussion and interpretation of the results. All authors critically revised the manuscript for intellectual content and approved the final version before submission. A.G.O. and L.B.C. have access to all the data and take responsibility for the data, accuracy of the data analysis, and the conduct of the research. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure statement

The authors report no conflicts of interest.

Data availability

Data sharing is not allowed according to Danish, Norwegian, Swedish law. Our own approvals to use the data sources for the current study do not allow us to distribute or make patient data directly available to other parties. Interested researchers may apply for Danish data access through the Research Service at the Danish Health Data Authority (e-mail: [email protected]; phone: [phone]). Up-to-date information on data access is available online (http://sundhedsdatastyrelsen.dk/da/forskerservice). Access to data from the Danish Health Data Authority requires approval from the Danish Data Protection Agency (https://www.datatilsynet.dk/english/legislation/). Similar options are available for data from the other countries.

Additional information

Funding

This work was partly funded by the National Cancer Institute; with Cancer Surveillance System data supported by Contract #HHSN261201300012I from the National Cancer Institute. This work was supported by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation. Funding for this work in Washington State, USA, was provided in part by the Alex Lemonade Stand Childhood Cancer Foundation and Contract # HHSN2612010000094P from the National Cancer Institute; with Cancer Surveillance System data supported by Contract #HHSN261201300012I from the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center; and Washington State Cancer Registry Data supported by the Centers for Disease Control.