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

Abstract

Importance: The 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 participants: In 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 (≤3 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 measures: Hazard 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.

Figure 1.. Identification of the Study Cohort

^aBased on Danish Cancer Registry data from 1996 to 2018.

Figure 2.. Childhood Central Nervous System (CNS) Tumors According to Maternal Use of Hormonal Contraception

All hazard ratios and incidence rate differences are adjusted for year of birth, and incident rate differences are presented per 100 000 person-years. Previous use refers to use more than 3 months before pregnancy start. Recent use refers to use 3 months or less before pregnancy start or during pregnancy, except for injections, implants, or intrauterine devices, with a different timeframe.

Figure 3.. Childhood Central Nervous System (CNS) Tumors According to Maternal Use of Progestin-Only Nonoral Contraceptive Type

All hazard ratios and incidence rate differences are adjusted for year of birth, and incident rate differences are presented per 100 000 person-years. ^aUse ≤1 year before pregnancy start to birth. ^bUse <3 years before pregnancy start to birth. ^cUse <5 years before pregnancy start to birth.