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No association between maternal use of the pill and CNS tumors in offspring

In a large-scale study in Danish children, no statistically significant association was found between maternal hormones contraception use and increased risk of central nervous system (CNS) tumors in their offspring.

The study was based on population-based registry data and included 1.1 million children aged 19 or younger born in Denmark between 1996 and 2014.

The study, conducted by Marie Hargreave, PhD, Danish Cancer Society Research Center, and colleagues, was published online today in the Journal of the American Medical Association.

Exposure to sex hormones in utero is a recognized cause of cancer in affected children, the authors note. In addition, the incidence of CNS tumors, among the most common and fatal types of childhood cancer, appears to be increasing. Therefore, they sought to determine if there could be a relationship between the two.

During a mean follow-up of 12.9 years, the team found that 725 children had been diagnosed with a CNS tumor (47.2% of women). The mean age at diagnosis was 7 years. The team noted that 11.5%, 65.7% and 22.8% of diagnosed children were born to mothers who had used recently, previously, or who had not used hormonal contraception, respectively.

The adjusted incidence rate for CNS tumors was 5.0 per 100,000 person-years for infants born to mothers who had recently used hormonal contraception (risk ratio [HR], 0.95), 4.5 per 100,000 person-years for children born to mothers who have already consumed (HR, 0.86) and 5.3 per 100,000 person-years for children born to mothers without consumption.

While recent use of implants (HR, 0.9) and intrauterine devices (HR, 1.5) showed no statistically significant association for the progestin-only non-oral hormonal contraception subgroups When evaluated, the team found that progestin-only injections were significantly associated with an increased risk. compared to no use (HR, 6.7). In addition, in all post hoc sensitivity analyzes, recent use of the main group of non-oral progestin-only products was significantly associated with CNS tumors.

The authors observe that an association between maternal use of injectable contraceptives and an increased risk of chromosomal abnormalities and major malformations in children has already been reported. These results for the injections, however, were based on a small number of cases, the likelihood test result was zero, and adjustments for multiple comparisons were not made. Although the results for this subgroup are confirmed, the authors point out, since CNS tumors in children are rare, high relative risk estimates would translate into small increases in absolute risk.

Although the large number of person-years and cancers increase statistical precision and the nationwide population-based design increases the generalizability of the results, the authors caution that the rarity of CNS tumors in children and the small number of cases in the studied cohort limits the subgroup analyzes and the statistical precision of some estimates.

In one accompanying editorial, Logan G. Spector, PhD, and Christopher L. Moertel, MD, of the University of Minnesota School of Medicine, and H. Irene Su, MD, of the University of California at San Diego, echo the findings authors and state: “Thus, women should be reassured about the use of hormonal contraception, including progestin-only injections, and the absence of any increased risk of CNS tumors in their offspring.”

The study was supported by the Danish Cancer Research Foundation, the Arvid Nilsssons Foundation, the Gangsted Foundation, the Harboe Foundation and the Johannes Clemmesens Foundation. Co-author Lina S. Mørch, PhD, said she received personal honoraria from Novo Nordisk as an employee from 2017 to 2019 and grants from Novo Nordisk for a collaborative research project outside of the submitted work.

Columnist Christopher Moertel, MD, said he received personal honoraria from OX2 Therapeutics, a University of Minnesota spin-off company that is involved in the development of brain tumor therapies.

JAMA. Published online January 4, 2022. Summary, Editorial

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