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A nationwide cohort study suggests an association between a woman’s use of hormonal contraceptives and leukemia in her offspring.

Children of mothers who used hormonal contraception, either during pregnancy or in the 3 months beforehand, had a 1.5-fold greater risk of leukemia, when compared to children of mothers who had never used hormonal contraception.

This increased risk translated to one additional case of leukemia per about 50,000 children exposed to hormonal contraceptives.

The increased risk appeared limited to non-lymphoid leukemia.

Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, Denmark, and her colleagues reported these findings in The Lancet Oncology.

The study included 1,185,157 children born between 1996 and 2014 and followed for a median of 9.3 years. Data on these children were collected from the Danish Medical Birth Registry and the Danish Cancer Registry.

The researchers looked at redeemed prescriptions from the Danish National Prescription Registry to determine the mothers’ contraceptive use and divided the women into three categories:

  • Mothers who had never used hormonal contraceptives
  • Those with previous hormonal contraceptive use, defined as greater than 3 months before the start of pregnancy
  • Mothers with recent contraceptive use, defined as during or within 3 months of pregnancy.

Results

There were 606 children diagnosed with leukemia in the study cohort—465 with lymphoid leukemia and 141 with non-lymphoid leukemia.

Overall, children born to mothers with previous or recent use of hormonal contraceptives had a significantly increased risk of developing any leukemia. The hazard ratios (HRs) were as follows:

  • Previous use of hormonal contraceptives—HR=1.25 (P=0.039)
  • Recent use—HR=1.46 (P=0.011)
  • Use within 3 months of pregnancy—HR=1.42 (P=0.025)
  • Use during pregnancy—HR=1.78 (P=0.070).

The risk of lymphoid leukemia did not increase significantly with maternal use of hormonal contraceptives. The HRs were as follows:

  • Previous use of hormonal contraceptives—HR=1.23 (P=0.089)
  • Recent use—HR=1.27 (P=0.167)
  • Use within 3 months of pregnancy—HR=1.28 (P=0.173)
  • Use during pregnancy—HR=1.22 (P=0.635).

However, the risk of non-lymphoid leukemia was significantly increased in children born to mothers with recent hormonal contraceptive use. The HRs were as follows:

  • Previous use of hormonal contraceptives—HR=1.33 (P=0.232)
  • Recent use—HR=2.17 (P=0.008)
  • Use within 3 months of pregnancy—HR=1.95 (P=0.033)
  • Use during pregnancy—HR=3.87 (P=0.006).

The association between recent contraceptive use and any leukemia was strongest in children ages 6 to 10 years. The researchers said this was not surprising because the incidence of non-lymphoid leukemia increases after the age of 6.

The researchers estimated that a mother’s recent use of hormonal contraceptives would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia over the study period.

This low risk of leukemia “is not a major concern with regard to the safety of hormonal contraceptives,” the researchers said.

However, the findings do suggest the intrauterine hormonal environment affects leukemia development in children, and this should be explored in future research.

This study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations, and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.


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