Maternal hormonal contraception and childhood leukemia: Is there a link?

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Children born to women who recently used any type of hormonal contraception were nearly 50% more likely to develop leukemia than children whose mother never used any contraception, according to a Danish nationwide cohort of roughly 1.2 million children born between 1996 and 2014. The authors cautioned, however, that their findings require validation before any change in clinical practice.

For the study, in The Lancet Oncology, researchers culled data from the Danish Medical Birth Registry and the Danish Cancer Registry, for which the registry recorded 606 children diagnosed with leukemia: 465 with lymphoid leukemia and 141 with non-lymphoid leukemia.

However, no association was found between the timing of hormonal contraception and risk for lymphoid leukemia. But for non-lymphoid leukemia, the risk was slightly more than double with use of contraception shortly before pregnancy and nearly four times as great for use during pregnancy.

The relationship between contraception and any type of leukemia was strongest for children diagnosed with the disease between ages 6 and 10.

But the child’s sex and perinatal factors barely influenced outcomes.

The investigators estimate that hormonal contraception use close to or during pregnancy probably resulted in one additional case of leukemia per roughly 50,000 exposed children, or 25 cases during the study period with a median follow-up of 9 years. 

“Previously, we had found a marked increased risk of leukemia in children born following the use of the specific hormone progesterone used in fertility treatment,” said principal investigator Marie Hargreave, PhD, a senior researcher in the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center in Copenhagen, Denmark. “Hence, the natural next step was to look at maternal use of hormones used in a different context than fertility treatment and the risk of childhood leukemia.”

Dr. Hargreave told Contemporary OB/GYN she was surprised that the findings were so strong, statistically significant, and consistent. “It is very difficult to identify risk factors for childhood leukemia, since it is fortunately such a rare disease,” she said. “When a disease is rare, it is difficult to obtain statistically significant findings because the statistical power to show true effects is limited. “

Despite validating the findings of the study, the precise mechanisms for a causal effect between contraception and childhood leukemia have yet to be determined.

“On the other hand, we know that the synthetic estrogen diethylstilbestrol (DES), which was used in the 1970s by pregnant women, caused cancer in offspring that had been exposed in utero,” Dr. Hargreave said.

Because the current study is the first large, well-conducted trial in this field, verification of the findings will be required by further large valid studies and possibly also animal models before changing clinical guidelines for use of hormonal contraception, according to Dr. Hargreave.

“On the positive side, we found that children born to women that stopped using hormonal contraception approximately 6 months prior to conception were not at an increased risk of leukemia,” she said.

But because there are still so few well-established risk factors for childhood leukemia, “it is not possible to share any recommendations at this time,” Dr. Hargreave said. “However, we are getting closer with our research, with the ultimate goal of preventing childhood cancer, which is one of the leading causes of mortality in children.”

Disclosures:

Dr. Marie Hargreave reports no relevant financial disclosures.