Maternal use of hormonal contraception and risk of childhood leukaemia: a nationwide, population-based cohort study

Abstract

Background: Maternal hormonal contraception has been suspected of being linked to an increased risk of childhood cancer. The aim of this study was to assess the association between maternal use of hormonal contraception and diagnosis of leukaemia in their children.

Methods: In this cohort study, we followed a nationwide cohort of 1 185 157 liveborn children between 1996 and 2014 listed in the Danish Medical Birth Registry and identified those diagnosed with leukaemia in the Danish Cancer Registry. Redeemed prescriptions from the Danish National Prescription Registry provided information about maternal hormonal contraceptive use, categorised as: no use (never used contraception before birth; reference category), previous use (>3 months before start of pregnancy), and recent use (≤3 months before and during pregnancy). We also calculated risk estimates separately for maternal hormonal contraceptive use during pregnancy. The primary outcome of interest was a diagnosis of any leukaemia in the children. Secondary outcomes were diagnoses of lymphoid leukaemia and non-lymphoid leukaemia. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for risk of leukaemia in children. The Data Protection Agency registration number for this study is 2017-41-5221.

Findings: Between Jan 1, 1996, and Dec 31, 2014, the 1 185 157 liveborn children accumulated 11 114 290 person-years of follow-up (median 9·3 years, IQR 4·6-14·2), during which 606 children were diagnosed with leukaemia (465 with lymphoid leukaemia and 141 with non-lymphoid leukaemia). Children born to women with recent use of any type of hormonal contraception were at higher risk for any leukaemia than children of women who never used contraception (HR 1·46, 95% CI 1·09-1·96; p=0·011); and for exposure during pregancy the risk was 1·78 (0·95-3·31; p=0·070). No association was found between timing of use and risk for lymphoid leukaemia (HR 1·23, 95% CI 0·97-1·57, p=0·089, for previous use and 1·27, 0·90-1·80, p=0·167, for recent use); however, the HRs for non-lymphoid leukaemia were 2·17 (1·22-3·87; p=0·008) for recent use and 3·87 (1·48-10·15; p=0·006) for use during pregnancy. Hormonal contraception use close to or during pregnancy might have resulted in one additional case of leukaemia per about 50 000 exposed children, or 25 cases during the 9-year study period.

Interpretation: Our findings suggest the maternal hormonal use affects non-lymphoid leukaemia development in children. Since almost no risk factors have been established for childhood leukaemia, these findings suggest an important direction for future research into its causes and prevention.

Funding: The Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation.