Association Between Maternal Hormonal Contraception Use and Central Nervous System Tumors in Children

Abstract

IMPORTANCEThe incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk.OBJECTIVE To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years). DESIGN, SETTING, AND PARTICIPANTSIn this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018).EXPOSURES Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (Յ3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered. MAIN OUTCOMES AND MEASURESHazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years. RESULTS After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, −0.3 [95% CI, −1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, −0.8 [95% CI, −1.7 to 0.0]) for previous use, compared with no use.No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception.CONCLUSIONS AND RELEVANCE Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Tom Nolan's research reviews—13 January 2022

“…A cohort study in JAMA provides further evidence that use of maternal hormonal contraceptives does not explain a rise in the incidence of CNS tumours in children since the 1970s. This large, prospective, population based study found no association between the two 5. It included all live-born children born in Denmark between 1995 and 2014—a total of 1 185 063 children—thereby winning this week’s prize for best population coverage in a research paper.…”

Maternal Contraceptive Use and Central Nervous System Tumors in Offspring

“…The report by Hargreave et al in this issue of JAMA demonstrated that most hormonal contraceptives used by the vast majority of women are not associated with CNS tumors in offspring. The isolated finding of a possible higher risk associated with progestin-only injections was based on very small numbers of cases, whereas no other progestin-only contraceptives, which may be expected to act similarly on cancer risk, showed an association with CNS tumors.…”

“…In this issue of JAMA , Hargreave et al examined the association between maternal hormonal contraception use and CNS tumors in their offspring. The authors used data from a population-based registry from Denmark and included 1185 063 children born between 1996 and 2014.…”

“…Second, if synthetic progestins do cross the placenta, the timing must be considered. Both the diethylstilbestrol and 17-α hydroxyprogesterone caproate examples involved repeated maternal exposure during pregnancy, while the study by Hargreave et al measured recent, shorter exposure, including prior to conception. The half-life of common progestins used in contraception ranges from 12 hours for levonorgestrel (used in intrauterine devices and combined hormonal contraception) to 24 hours for medroxyprogesterone (MPA; used in injectable contraception).…”

“…Whether progesterone receptors are expressed in each of the cell types or locations vulnerable to carcinogenic transformation is unclear. One difficulty in examining a rare disease is the small number of cases; in the study by Hargreave et al, the type(s) of CNS tumors that comprised the excess cases among those exposed to progestin-only injections could not be presented. To fully assess the plausibility of progestin as a potential cause of specific brain tumors, the biology of specific populations of cells of origin would need to be examined.…”